Biotech Ideas

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>>> Iovance Biotherapeutics, Inc. (IOVA), a clinical-stage biotechnology company, focuses on developing and commercializing cancer immunotherapy products to harness the power of a patient's immune system to eradicate cancer cells. It has six ongoing phase 2 clinical studies, including C-144-01, of its lead product candidate, lifileucel, for the treatment of metastatic melanoma; C-145-04, of its product candidate lifileucel for recurrent, metastatic, or persistent cervical cancer; and C-145-03, of its product candidate LN-145, for recurrent and/or metastatic head and neck squamous cell carcinoma. Iovance Biotherapeutics, Inc. has collaborations and licensing agreements with H. Lee Moffitt Cancer Center; M.D. Anderson Cancer Center; Ohio State University; Centre hospitalier de l'Université de Montreal; Cellectis S.A.; and Novartis Pharma AG. The company was formerly known as Lion Biotechnologies, Inc. and changed its name to Iovance Biotherapeutics, Inc. in June 2017. Iovance Biotherapeutics, Inc. was incorporated in 2007 and is headquartered in San Carlos, California. <<<



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[gfp927z]

Blade, Thanks for the stock ideas, I'll check them out :o)


>> Lindsay Rosenwald <<


I remember the name from years ago, but not the details, but it turns out we were both at Temple Univ at the same time (early 1980s), and a neighbor of mine who became a cardiologist would have been there with Lindsey Rosenwald, so 'small world' :o)



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>>> Mersana Therapeutics, Inc. (MRSN), a clinical stage biopharmaceutical company, develops antibody drug conjugates (ADC) for cancer patients with unmet need. It develops XMT-1592, a Dolasynthen ADC targeting NaPi2b-expressing tumor cells, which is in phase I clinical trial for the treatment of ovarian cancer and NSCLC adenocarcinoma. The company also develops XMT-1660, a B7-H4-targeted Dolasynthen ADC candidate; and XMT-2056, an immunosynthen development candidate. It has a strategic research and development partnerships with Merck KGaA and Asana BioSciences, LLC for the development of ADC product candidates utilizing Fleximer. The company was formerly known as Nanopharma Corp. and changed its name to Mersana Therapeutics, Inc. in November 2005. Mersana Therapeutics, Inc. was incorporated in 2001 and is headquartered in Cambridge, Massachusetts. <<<





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[bladerunner1717]

gfp,

Sorry to hear about your friend; knee surgery is supposed much more difficult than hip surgery. My orthopedic surgeon did over 1,650 hip and knee replacements last year. Hard to believe, huh?

Beyond JSPR, I like CRIS, CRDF, possibly KZIA. I own all of those. I like MBIO a lot, but it's a Lindsey Rosenwald company, so I'm very hesitant. I also like IOVA and especially MRSN.

Bladerunnerr

[gfp927z]

Blade, GL with your hip recovery :o) Another poster is having his knee done soon, so at this rate we'll all be quasi 'androids', but thank goodness for modern technology :o) I knew an orthopedic surgeon who has done hundreds / thousands of these procedures, and they have it down to a routine, although he said hips can still be challenging.

For the stock market, 2023 isn't looking too great at the moment, but the 4% from the money market and T-Bills is a good alternative for now. My gunslinging days are over, though it's still fun to follow the various sectors and some bio stocks. HALO and XENE seem like solid long term picks. I remember HALO from years ago, but had no idea it would become a 10 bagger. SGEN I remember from the IMGN days, and they turned out to be the big winner in the 'armed MAB' space. JSPR has similar mega potential if things continue to go well in the clinic. Just curious about your other current favorites? Thanks.

AMAM seems interesting, tiny but they have lots of cash, a proprietary platform, and some intriguing recent breast cancer data -

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=170723982



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[bladerunner1717]

JSPR was up over 800% this morning, but has fallen back.

The bigger news may come later this quarter.

[quote
Continued progress on the registrational study of JSP191 in older, transplant-eligible patients with AML/MDS: Jasper held a Type B meeting with the FDA during which a review of the trial comparator arm, population, size, statistical assumptions, and primary endpoints were discussed. The Company agreed with the FDA to submit a trial protocol that will allow a potential initiation of a registrational study in AML and MDS patients undergoing stem cell transplant.

Upcoming clinical and corporate milestones:

Initiate a new study of JSP191 as second-line therapy for patients with lower-risk MDS expected to start in the first quarter of 2023

Initiate a registrational study in AML/MDS patients undergoing stem cell transplant in the first quarter of 2023][/quote]

Bladerunner

[gfp927z]

Blade, Thanks. Sounds great, and looks like their drug has a broad range of other conditions it can potentially treat. Still early, but sounds like it could be really big. Just curious if your oncologists have been following Briquilimab's clinical progress? Thanks. Hope you are having a nice holiday season :o)

Btw, one bio I follow loosely (AXSM) finally got FDA approval for their faster acting antidepressant combo drug (Auvelity), which has a chance of taking a sizable chunk of a huge market. While bio gurus like Dew have largely avoided the stock (Auvelity is merely a combination of two existing drugs), the drug works very quickly, in contrast to the current SSRI related drugs. The components of Auvelity are well known existing drugs, so the safety profile is well characterized, and docs should be eager to give it a try. Current SSRI related drugs take numerous weeks before they start working, and a significant number of patients get little or no benefit, plus they have the black box warning problem. Anyway, looks like AXSM could be a decent long term holding, and has been largely de-risked, and they also have a nice pipeline of other drugs. No longer a microcap, but could still be multi-bagger over the longer term, and a potential acquisition target.


>>> To date, briquilimab has a demonstrated efficacy and safety profile in 130 dosed subjects and healthy volunteers, with clinical outcomes as a conditioning agent in severe combined immunodeficiency (SCID), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), Fanconi anemia (FA), and sickle cell disease (SCD). In addition, briquilimab is being advanced as a transformational non-genotoxic conditioning agent for gene therapy and as a primary therapeutic in low-risk MDS patients. Clinical studies also suggest briquilimab can be used as a primary therapeutic to treat mast cell diseases such as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), and allergic asthma. <<<



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[bladerunner1717]

JSPR up 330% on this news. (It has since fallen back a bit.)



GlobeNewswire
Jasper Therapeutics Announces Positive Clinical Data from a Phase I/II Trial of Briquilimab as a Conditioning Treatment in Sickle Cell Disease and Beta Thalassemia
Jasper Therapeutics
Tue, January 3, 2023 at 5:00 AM PST·7 min read
In this article:

JSPR
+320.6984%

Jasper Therapeutics
Jasper Therapeutics
All three sickle cell disease participants treated with briquilimab successfully engrafted with neutrophil engraftment within 12-16 days

First two participants with peripheral blood chimerism at 60 days after allogeneic stem cell transplant achieved 100% donor myeloid chimerism

First participant treated has a total hemoglobin level of 13.3 g/dL at five months follow up, increased from 8-9 g/dL at baseline

REDWOOD CITY, Calif., Jan. 03, 2023 (GLOBE NEWSWIRE) -- Jasper Therapeutics, Inc. (NASDAQ: JSPR), a biotechnology company focused on transforming the field of hematopoietic stem cell therapies, today announced positive clinical data from the first three participants in an investigator-initiated Phase 1/2 clinical trial (NCT05357482) evaluating the addition of briquilimab (formerly known as JSP191), Jasper’s anti-c-KIT monoclonal antibody, to an existing bone marrow transplantation regimen (NCT00061568) in individuals with sickle cell disease (SCD) and beta thalassemia considered at high risk for complications from or ineligible for standard myeloablative hematopoietic stem cell transplant. The addition of briquilimab is being studied as a potential way to achieve a higher percentage of healthy donor stem cell engraftment (donor chimerism) without increased toxicity. The Phase 1/2 clinical study is led by Dr. John F. Tisdale, Director of the Cellular and Molecular Therapeutics Laboratory, NHLBI.

“While stem cell infusion with healthy donor stem cells or gene-corrected cells are potentially curative options for SCD and beta thalassemia, they are both limited by the toxicity of current conditioning regimens using busulfan or melphalan, which are often cited as the most concerning safety risks for transplant patients and physicians,” said Ronald Martell, President and CEO of Jasper Therapeutics. “With briquilimab, we hope to offer a highly targeted conditioning regimen to directly address conditioning toxicity as a barrier limiting the ability of patients to access curative hematopoietic stem cell therapies.”

For SCD and beta-thalassemia, transplantation of healthy donor stem cells is a multi-step process. After donor cells are collected, a human subject’s existing stem cells must be cleared from the bone marrow to make space for the transplanted cells, which is known as bone marrow conditioning. Next, the newly transplanted cells must survive and replicate within the bone marrow, which is known as bone marrow engraftment. The extent of engraftment is measured by the proportion of the donor cells and the human subject’s own cells, which is known as donor chimerism. As has been shown, improving chimerism is crucial to lead to a sufficient proportion of healthy donor stem cells that produce healthy red blood cells and reverse the sickle phenotype after the stem cell transplant.

The primary objective of the study is to determine if the addition of briquilimab would increase the proportion of patients with donor myeloid chimerism ≥98% at 1-year post-transplant. Briquilimab has the potential to improve disease-free survival in combination with low-dose irradiation as part of a transplant conditioning regimen. The study is currently actively enrolling at NHLBI.

In this study, briquilimab was added to the regimen used at NHLBI consisting of alemtuzumab, low-dose irradiation, and sirolimus prior to infusion of mobilized peripheral blood cells from human leukocyte-antigen matched related donors. All three sickle cell study participants treated with briquilimab have successfully engrafted with no briquilimab-related severe adverse events observed. Participant 1 achieved neutrophil engraftment at 12 days after transplant and platelet engraftment at 17 days after transplant. Participant 2 achieved neutrophil engraftment at 12 days and platelet engraftment at 10 days. Participant 3 achieved neutrophil engraftment at 16 days and platelet engraftment at 8 days. Both of the first two participants with peripheral blood chimerism achieved 100% donor myeloid chimerism at 60 days post-transplant. At five months post-transplant, the first participant treated with briquilimab has a total hemoglobin of 13.3 g/dL, increased from 8-9 g/dL at baseline.

About Briquilimab (formerly known as JSP191)

Briquilimab is a targeted, monoclonal antibody that inhibits the cell-surface receptor c-KIT, also known as CD117. It is currently being evaluated as a conditioning agent for cell and gene therapies, as well as a standalone therapy. To date, briquilimab has a demonstrated efficacy and safety profile in 130 dosed subjects and healthy volunteers, with clinical outcomes as a conditioning agent in severe combined immunodeficiency (SCID), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), Fanconi anemia (FA), and sickle cell disease (SCD). In addition, briquilimab is being advanced as a transformational non-genotoxic conditioning agent for gene therapy and as a primary therapeutic in low-risk MDS patients. Clinical studies also suggest briquilimab can be used as a primary therapeutic to treat mast cell diseases such as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), and allergic asthma.

About Jasper Therapeutics

Jasper Therapeutics is a clinical-stage biotechnology company focused on unlocking access to curative therapies by targeting and eliminating diseased stem cells. Jasper’s lead program is briquilimab, a first-in-class monoclonal antibody targeting c-KIT (CD117), an important receptor found on stem cells and mast cells. In parallel, Jasper is advancing its mRNA cellular programming platform which is designed to overcome key limitations of allogeneic and autologous gene-edited stem cell grafts by transiently modifying stem cells with mRNA, augmenting them to treat several diseases of the blood and bone marrow. Both innovative programs have the potential to enable curative therapies to a greater number of patients with life-threatening cancers, genetic disorders, and inflammatory diseases. For more information, please visit us at jaspertherapeutics.com.

Bladerunner

[gfp927z]

Another young athlete drops from a heart attack, this time on Monday Night Football. With 15-20 million Americans watching tonight's game, it will be hard for the controlled media to make this event disappear 'down the memory hole', though they'll undoubtedly try.

The Covid vaccines have known cardiovascular effects like pericarditis, myocarditis, and
arrhythmias, particularly in young males. Covid itself likewise has cardio effects, blood clots, etc. A 37 year old ABC executive producer recently died of a heart attack, but nothing to see here folks, go back to sleep -


>>> At least 69 athletes collapse in one month, many dead

The reports of athletes who suddenly collapse have been increasing noticeably lately. Heart problems such as heart inflammation are often the cause – one of the known life-threatening side effects of Covid vaccines, which even the manufacturers themselves warn against.

November 26, 2021


https://dpbh.nv.gov/uploadedFiles/dpbhnvgov/content/Boards/BOH/Meetings/2021/Public%20Comments%20324%20to%20328.pdf


The current phenomenon is also evident if you simply look on Wikipedia at the list of footballers who have collapsed and died. The year 2021 stands out with 13 entries so far. In no other year mentioned have more footballers died during a game. And this list goes back to the year 1889. So it really is a historical event.

The mainstream media is curiously uninterested in this major global story. The German online outlet Wochenblick compiled a referenced list of the cardiac incidents in October while another online outlet Granite Grok published a new list of sportsmen collapsing on the field. Other outlets also listed these incidents, with some cases overlapping.

But these do not include Filipino professional basketball star Roider Cabrera who on Wednesday collapsed
during tournament play in Pasig City. The Tribune from the Philippines reported he had a cardiac arrest. Roider Cabrera later lost consciousness inside the locker room before he was immediately rushed to hospital where he was diagnosed with fatal arrhythmia according to a local news.

Many top athletes from both Europe and the US have reported serious side effects after a Covid jab. For
French professional tennis player Jérémy Chardy, it has meant the end of his career. Chardy, formerly ranked
73 in the world, said he has been unable to train and play. “Since I got my vaccine [between the Olympics and
the US Open], I have a problem, I have a series of problems. As a result, I can’t train, I can’t play.”

Icelandic professional footballer Emil Pálsson (28) collapsed in the game between his club Sogndal IL and
Stjørdals/Blink. As reported by German daily Bild, Pálsson collapsed during the game, according to the Norwegian broadcaster NRK and the newspaper Verdens Gang. According to his club, he suffered cardiac arrest and had to be resuscitated.

This week, on November 24, in the middle of the second half of the game between Reading FC and Sheffield
United, Sheffield player John Fleck (30) suddenly collapsed on the field due to a cardiac incident and had to
be rushed to hospital.

Soccer star from Sheriff Tiraspol Adama Traore went down while holding his chest during the Champions

League game against Real Madrid on Wednesday night.
In Montana, a Park City High School football player Jedd Hoffman, passed away this month, almost one week after collapsing on the field during practice. These are cases not yet listed in the ongoing carnage that the jabs
have unleashed.

In October cardiac and circulatory events on the sportsfield went through the roof

Below is a shockingly long list of athletes who collapsed last month from heart problems or circulatory disorders such as strokes. Unfortunately, some of these incidents were fatal for the often very young athletes. The numbers are alarming, especially in view of mandatory Covid shots.

(1) At the encounter between PGS E Bosico and Romeo Menti (Allerona Scalo) in Umbria/Italy on October 2,
2021 , a “young player” from the visiting team collapses without any external influence and is transported to the
hospital.

(2) Martin Lefèvre (16) from FC Agneaux collapses without any previous illnesses with a stroke during the game
against FC Saint-Lô Manche on October 2, 2021. He is paralyzed on one side and has no ability to speak.

(3) Niels de Wolf, 27, from the Belgian football club White Star Sombeke, suffered a cardiac arrest immediately
after the game against Verrebroek on October 3, 2021, was resuscitated with a defibrillator, but died in hospital
on October 6, 2021.

(4) Arcisate, Province of Varese, Italy: The amateur match between Valceresio and Tradate (Prima Categoria,
Girone A) is canceled after 20 minutes after the referee suffers a medical emergency . Message from October 3,
2021.

(5) Timucin Sen from Germania Großkrotzenburg will be substituted on October 3, 2021 in the game against
Spvgg. Oberrad. He collapsed after ten minutes into the game and was taken to a clinic in Gelnhausen.

(6) On October 3, 2021, referee Öner Calik, in his mid-30s, canceled the game between VfB Waltrop II and
Vinnum II due to his own health problems and was taken to the hospital by the emergency doctor.

(7) On October 4 , 2021, a person in charge of SV SW Frömern collapsed on the field before the game against
Kamener SC.

(8) Cleveland, Ohio, USA: Elias Abou Nassif (44) suffers cardiac arrest in the gym and can be saved by using a
defibrillator. Message from October 5, 2021

(9) Lecco (Italy), October 7, 2021: 17-year-old athlete from Colverde collapses during training with cardiac
arrest. Defibrillator insert. He is now fighting for his life in the intensive care unit at Lecco Hospital.

(10) AH player (49) from SC Massay in France suffers a fatal heart attack during a game on October 8, 2021.

(11) The golf caddy Alberto Olguín from Mexico collapses dead on the ninth hole of the tournament in Nuevo
Vallarta (Mexico). Message from October 9, 2021.

(12) England: In the League One game between Ipswich Town and Shrewsbury on October 9, 2021, Shrewsbury
professional striker Ryan Bowman (29) has to be taken off the field after a good half hour of play with extreme
cardiac arrhythmias and a pulse of 250 and treated with a defibrillator.

(13) Pompeo Tretola, an 18-year-old soccer player from FC Matese, collapses during the game against Vastese
Calcio on 10.10.2021 without any warning signs. He is later transported to the hospital.

(14) Normandy, France: After warming up before the match between Saint-James and Avranches on 10 October
2021, 40-year-old player from Saint-James suffers a heart attack and is saved by a fire-medic on the team of
Avranches.

(15) 59-year-old long-distance runner from Biella dies of heart failure in a race in northern Italy. Message from
10/10/2021.

(16) In the match between Wacker Mecklenbeck and Fortuna Freudenberg in the Women’s Westphalia League
on October 10, 2021, a player collapsed without any opposing influence and was transported to the Münster
University Hospital.

(17) Argentina: Mayor Guillermo Mercado (50) died of cardiac arrest after participating in the long-distance run
“Aventura de Cerezal” . Message from 10/11/2021.

(18) At the Boston Marathon on October 11, 2021, marathon star Megan Roth collapsed after eight miles of
racing with cardiac arrest. She can be saved and is waiting for a defibrillator to be implanted.

(19) NBA player Brandon Godwin of the Atlanta Hawks explains that the Covid vaccination had caused severe
side effects for him, which would mean that he not only had to end the season, but possibly his entire career.
Message from October 12, 2021.

(20) Le Havre, France: A 27-year-old policeman suffers a fatal heart attack while jogging. News from October
12, 2021.

(21) Ferran Duran, player from the 4 Catalan League (27), suffered cardiac arrest five times during a game on
October 12, 2021 and miraculously survived.

(22) France: The player Christophe Da Silva of Saint Avé collapses with cardiac arrest in the AH Cup match
between the Locqueltas footballers and Saint Avé . Message from 10/13/2021

(23) Ensenada, Mexico: The 16-year-old student Héctor Manuel Mendoza dies of a “fulminant heart attack” while training in a sports club . Message from 10/13/2021.

(24) Brazil: Atletico Goianiense ‘s youth footballer Fellipe de Jesus Moreira suffers a heart attack in the training
center and later another heart attack in the emergency room. Now he is fighting for his life in the intensive care
unit. News from October 14, 2021.

(25) The next referee who breaks down and dies during a game : happened at the Kreisliga B game between SC
Daisbach and FSV Taunusstein in Aarbergen on the evening of October 14, 2021.

(26) The professional cyclist and multiple Italian time trial champion Gianni Moscon (27) is about to have a
catheter ablation due to cardiac arrhythmia. News from October 14, 2021.

(27) Joe Plant from Whitby (Yorkshire, England) suffers in 2021 at a race walking competition of all the British
Heart Foundation a cardiac arrest, at 14:10, he himself reported.

(28) Lars Schneider, trainer of TV Braach, retires due to lack of strength after he collapsed with cardiac
arrhythmias during the game of the district league A Hersfeld / Rotenburg against SG
NentershausenWeißenhasel-Solz in Solz and had to be transported to the clinic. Message from 10/14/2021.

(29) Treviso, Italy: 53-year-old AH player suffers a heart attack while training on October 14, 2021 . He could be
kept alive by fellow players.

(30) Australia: 14-year-old student Ava Azzopardi suffers cardiac arrest during the game between Runaway Bay
and Magic United at Surfers Paradise Apollo Soccer Club. She is resuscitated by nine rescue workers, put into an
artificial coma and is now fighting for her life in the hospital. News from October 15, 2021.

(31) At the handball 3G Bundesliga game in Wuppertal between Bergisches HC and HSG Wetzlar on October 16
, 2021 , a spectator with cardiac arrest collapsed not only during the game (this led to the game being
abandoned); after the game, a second spectator also suffered a cardiac arrest .

(32) A 16-year-old boy from Idaho collapses when lifting weights with cardiac arrest. He wakes up after two days
in a coma, but is “extremely confused” and has no short-term memory. News from October 16, 2021.

(33) Camposampiero, Province of Padua, Italy: The 37-year-old doctor Filippo Morando dies while jogging. The
ambulance flown in by helicopter can no longer do anything as it is too late. Message from 10/17/2021.

(34) The Premier League game between Newcastle United and Tottenham FC on October 17, 2021 was
suspended due to a medical emergency in the stands.

(35) Haitem Jabeur Fathallah, 32, a Fortitudo Messina basketball player, suffers cardiac arrest during the game
and dies in hospital. Message from 10/17/2021.

(36) Blumenau, Brazil: Former FC Brusque soccer player from the Brazilian second division, Adans Joao Santos
Alencar (38) , suffers a fatal cardiac arrest in a footvolley tournament. Message from 10/17/2021.

(37) Lombardy, Italy: A 40-year-old cyclist stops because of “medical emergency” on , falls to the ground, is
transported to the hospital by rescue helicopter Rho. Message from 10/17/2021.

(38) Waseem Aslam of Bradford (England) interrupts a game of football suffering from a cardiac arrest. He
could be saved by friends. Message from October 18, 2021.

(39 ) A 26-year-old runner collapses from cardiac arrest in the Detroit Free Press Marathon . Two police officers
rescue him with chest compressions. After that he was treated in the hospital. Message from October 19, 2021.

(40) Cardiac arrhythmias force soccer star Sabrina Soravilla to end her career on October 19 , 2021 after 68
international matches for Uruguay.

(41) Real Murcia’s Antonio López had to retire at the age of 32 due to a heart disease . Message from October 19,
2021.

(42) A 41-year-old amateur soccer player in Brazil dies of cardiac arrest in a game. It happened on October 19,
2021 in Nao-me-toque (Rio Grande do Sul).

(43) Henry, a teenager from Halifax, England, is recognized for saving the life of his 56-year-old father after a
cardiac arrest while jogging in March. Message from October 20, 2021.

(44) At the first division match between Osasuna and Granada in Pamplona on October 22, 2021, a home team
fan suffers cardiac arrest and dies in hospital.

(45) Dieppe, France: A jogger collapses while running with cardiac arrest. He is rescued by two police officers on
the patrol. Message from 10/22/2021.

(46) Acerra (Italy): Remigio Gova. A basketball referee and nurse, in Italy inevitably “vaccinated” against Covid,
at only 30 years of age “died in his sleep”. Message from October 23, 2021.

(47) A double medical emergency at an English stadium on 10/23/2021 during the Championship League game
between West Brom and Bristol City. Defibrillator used, the game had to be postponed twice.

(48) Belgian soccer player (37) suffered cardiac arrest in the locker room after his club’s match on October 24th,
2021, was reanimated but died in hospital.

(49) France: 43-year-old US Montgascon goalkeeper dies of cardiac arrest at half-time. Happened on October
24, 2021 at the La Bâtie-Montgascon stadium.

(50) A 53-year-old suffers a triple cardiac arrest in Bilbao half-marathon and passes away as a result. Message
from October 24, 2021.

(51) Tevita Brice, 28, of Montclair Rugby Football Club, US, collapsed on the pitch with a heart attack. In critical
condition. Message from 10/25/2021.

(52) Fatal cardiac arrest at a mountain running event in the Italian Alps on October 24, 2021. The victim is
Bruno Taffarel (56) from Cordenons.

(53) A cardiac arrest of a player overshadowed the top game of the A2 Dortmund regional soccer league. The
player from SG Gahmen was hospitalized on 10/24/2021. The affected team had played against Eving Selimiye
Spor.

(54) Nocera Umbra, Italy: Sports teacher and soccer coach Mario Mingarelli suffered fatal cardiac arrest during
his team’s game on October 24, 2021 at the age of 69 .

(55) The amateur match between Frugesport (Ravenna) and Vaccolino (Prima Categoria, Girone F) is canceled
after 32 minutes because the “young” referee suffers a medical emergency . Message from 10/26/2021.

(56) 17-year-old Elly Böttcher from Rostocker FC collapsed unconscious during the away game in Hohen
Neuendorf of the Frauen Regionalliga Nordost on October 24, 2021 without any interference and was
transported to the hospital. The game was stopped after the incident.

(57) A 20-year-old Italian collapses when skateboarding with a cardiac arrest and is now fighting for his life in
the hospital in Verona, where he was transported by helicopter. News from October 25, 2021.

(58) A fan of the Belgian second division team from Lier collapsed on October 27, 2021 in the stadium with
heart problems and died in hospital.

(59) On the same day (27.10.2021) also in Belgium, the cup match against Dender of Eupen: A fan collapses
with cardiac arrest and must be revived.

(60) Sassuolo, Italy: A 53-year-old mountain biker suffers fatal cardiac arrest on an off-road tour. Message from
10/27/2021.

(61) England: A fan collapses after the Cup game Stoke City against Brentford on October 27, 2021 in front of
the stadium with cardiac arrest and dies.

(62) A player from Blau-Weiß Linz from Ghana (26) collapses during his club’s home game against Hartberg
and is transported to the hospital. Happened on October 27, 2021 at the round of 16 for the ÖFB-Pokal. He is
diagnosed with a congenital heart rhythm disorder and was helped with a defibrillator.

(63) Pakistan: The 30-year-old player Muhammad Islam from FC Raziq Chaman suffers a heart attack in the
middle of the game against Millat Club and dies. Message from 10/28/2021.

(64) The Swedish-Iraqi player Aimar Sher from the Italian first division club Spezia Calcio collapses during
training and is transported to the hospital. Message from 10/28/2021.

(65) Pennsylvania, USA: A 12-year-old student at Chartiers Valley Middle School collapses while playing
basketball in physical education class without help and dies. Message from 10/28/2021.

(66) Barcelona star Sergio Aguero (33) suddenly gets breathless during the league game against Deportivo
Alaves, grabs his chest and collapses. The Argentine national team player must now take a break of at least three
months. A few months ago he was suffering from a severe Corona infection. Notification from 10/30/2021

(67) During the ICE ice hockey league game, Boris Sadecky (24) from the Bratislava Capitals collapses on the ice without any outside interference. He dies five days later. It later emerges that he suffered from “mild
myocarditis” on match day. Message from 10/30/2021

(68) The student and soccer coach for the La Salle High School team in Pennsylvania, USA Blake Barklage died
after a heart attack over the weekend. Message from 11/1/2021.

(69) Argentina: The soccer player Ronald Biglione dies after the 2nd vaccination due to thrombosis – a wellknown side effect of the vaccinations against which the manufacturers themselves warned about. He was treated in Cordoba hospital for two weeks. Message from November 5, 2021.

<<<



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[gfp927z]

>>> GABAkines -


https://finance.yahoo.com/news/respirerx-pharmaceuticals-inc-announces-entry-134500660.html


Under a License Agreement with the University of Wisconsin-Milwaukee Research Foundation, Inc. (“UWMRF”) and on behalf of its EndeavourRx business unit, RespireRx has licensed rights to certain selectively acting GABAkines because of their ability to selectively amplify inhibitory neurotransmission at a highly specific, subset of GABAA receptors, thus producing a unique efficacy profile with reduced side effects. Preclinical studies have documented their efficacy in a broad array of animal models of interrelated neurological and psychiatric disorders including epilepsy, pain, anxiety, and depression in the absence of or with greatly reduced propensity to produce sedation, motor-impairment, tolerance, dependence and abuse. The Company currently is focusing on developing KRM-II-81 for the treatment of epilepsy and pain.

KRM-II-81 has displayed a high degree of anti-convulsant activity in a broad range of preclinical studies, including in treatment resistant and pharmaco-resistant models. Not only was KRM-II-81 highly effective in these models, but pharmaco-resistance or tolerance did not develop to its anti-convulsant properties. These latter results are particularly important because pharmaco-resistance occurs when medications that once controlled seizures lose efficacy as a result of chronic use and it is a principal reason some epileptic patients require brain surgery to control their seizures. In support of its potential clinical efficacy, translational studies have demonstrated the ability of KRM-II-81 to dramatically reduce epileptiform electrical activity when administered in situ to brain slices excised from treatment resistant epileptic patients undergoing surgery.

In addition, KRM-II-81 has displayed a high degree of analgesic activity in a broad range of preclinical studies. In intact animal models of pain, the analgesic efficacy of KRM-II-81 was comparable to or greater than commonly used analgesics. At the same time, KRM-II-81 did not display side effects such as sedation and motor impairment, but even more importantly, it did not produce tolerance, dependence, respiratory depression or behavioral changes indicative of abuse liability, which are produced by opioid narcotics and are at the heart of the opioid epidemic.

<<<



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[gfp927z]

Axsome Therapeutics - >>> 3 Fierce Stocks That Are Screaming Buys in December


By Sushree Mohanty

Dec 7, 2022

Motley Fool


https://www.fool.com/investing/2022/12/07/3-fierce-stocks-that-are-screaming-buys-in-decembe/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article


Axsome Therapeutics (AXSM 1.21%) has soared this year, gaining 103% and outperforming the market. This surge is being driven by expectations that sales of its two new drugs will skyrocket in the coming years, as well as its recent excellent quarterly results.

Sunosi, acquired from Jazz Pharmaceuticals in May, has been Axsome's best-selling product. It is used to treat narcolepsy-related excessive daytime drowsiness. In the third quarter, the drug generated $16.8 million in net sales in the U.S.

Another one of its products, Auvelity, which is now available by prescription, was launched in the U.S. in October. In August, the U.S. Food and Drug Administration (FDA) approved this medication to treat depression or major depressive disorder (MDD).

Given the rise in MDD diagnoses since the pandemic started, this medication may completely alter the game for Axsome. These two medications could significantly increase Axsome's revenue once they are made available on international markets.

Axsome is also working on several intriguing products. A clinical trial for AXS-05 to treat MDD, smoking cessation, and agitation associated with Alzheimer's disease (AD) is currently in its second phase. Axsome may reach new heights once products like AXS-07 (to treat migraines), AXS-12 (a potential therapy for narcolepsy), and AXS-14 (to manage fibromyalgia) hit the market.

The company's finances are adequate to support its current and future pipelines. It had $227 million in cash at the end of the third quarter. Management believes that its current cash reserves and "remaining committed capital under the $300 million term credit facility" will be enough to cover projected plans through 2025.

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>>> Ambrx Biopharma Inc. (AMAM), a clinical-stage biologics company, discovers and develops engineered precision biologics using its proprietary expanded genetic code technology platform. Its lead product candidate is ARX788, an anti-HER2 antibody-drug conjugate (ADC), which is investigated in various clinical trials for the treatment of breast cancer, gastric/gastroesophageal junction cancer, and other solid tumors, including ongoing Phase 2/3 clinical trials for the treatment of HER2-positive metastatic breast cancer and gastric cancer.

The company is also developing two earlier-stage product candidates, including ARX517, an anti-PSMA ADC, which is in a Phase 1 clinical trial for the treatment of prostate cancer and other solid tumors; and ARX305, an anti-CD70 ADC in investigational new drug-enabling studies for the treatment of renal cell carcinoma and other cancers. In addition, it is developing other multiple product candidates targeting immuno-oncology applications, which include ARX822, a fab-small molecule bispecific that is in preclinical development for cancers; and ARX102, an immuno-oncology IL-2 pathway agonist to stimulate the patient's own immune system by targeting the ß and gamma receptors on the cytotoxic T cell.

Ambrx Biopharma Inc. has collaborations with Bristol Myers Squibb Company; AbbVie Inc.; BeiGene; Sino Biopharmaceutical Co., Ltd.; NovoCodex; and Elanco Animal Health. The company was incorporated in 2003 and is headquartered in La Jolla, California.

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https://finance.yahoo.com/quote/AMAM/profile?p=AMAM


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Ambrx BioPharma - >>> Meet the Biotech Stock That Jumped Over 1000% in One Day


TipRanks

December 11, 2022


https://finance.yahoo.com/news/meet-biotech-stock-jumped-over-173724936.html


Investors looking for some unseemly gains will often pivot to the biotech space, a segment for which the term high-risk/high-reward might possibly have been coined. Bear or bull, it can make no difference to these names, which can soar or crash, depending on specific events such as regulatory approval/rejection or strong/disappointing results from a clinical trial.

Even so, the gains posted by Ambrx Biopharma (AMAM) in Friday’s session are unusual and particularly eye-catching. The stock soared to the tune of a hardly believable 1007% after the company announced pleasing results from the mid-stage testing of its breast cancer drug ARX788.

In the Phase 2 ACE-Breast-03 study, which took place in the U.S., Korea, and Australia, the drug was assessed as a treatment for HER2-positive mBC (metastatic breast cancer) patients who are resistant or refractory to T-DM1.

The preliminary results showed a 51.7% overall response rate (ORR) and 100% disease control rate (DCR) following treatment with ARX788. Additionally, no drug-related serious adverse events (SAEs) were noted by any patients.

With investors reacting the way they did, it’s safe to say they were impressed with the results; considering how big the breast cancer market is, the drug’s potential has caused a bit of a stir.

Cowen analyst Phil Nadeau also likes what he’s seeing here, noting: "ARX-788 continues to have a good safety profile with no AEs leading to discontinuation or drug-related SAEs. Our consultants have called ARX788's activity in HER2 pretreated patients 'robust' and think that its activity in Enhertu and Kadcyla failures in particular is likely to ensure ARX788 a place in the treatment paradigm."

It should be noted, the results are preliminary and that it is still a mid-stage trial and further Phase 3 testing will be required, although given the strong results, the company might decide to try and fast-track this drug to approval.

Meanwhile, Amrbrx's partner NovoCodex Biopharmaceuticals is currently overseeing Two Phase 3 studies and one registration-enabled Phase 2 study with ARX788 in China. Data readouts are expected next year.

For Baird analyst Joel Beatty, the investment thesis for AMAM hinges on a “relatively large number of shots on goal compared to other biotech companies of its market cap.”

“Within the company's cash runway into 2025, we should get phase 1b/2 data for ARX 517 (anti-PSMA) and ARX 305 (anti-CD70),” Beatty elaborated. “Also, Ambrx's partnerships with NovoCodex, SIno Biopharm and BeiGene provide additional shots on goal.”

Overall, Ambrx has slipped under most analysts’ radar; the stock’s Moderate Buy consensus is based on just two recent Buy ratings. The average price target stands at $4, which is `~12% lower than its current value -- most likely a result of Friday's huge surge.

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>>> Amgen Delves Further Into Immune Therapies With Horizon Deal


Bloomberg

Dec 2022

by Dinesh Nair, Katie Roof and Angelica Peebles


https://www.msn.com/en-us/money/companies/amgen-to-buy-horizon-therapeutics-in-27-8-billion-deal/ar-AA15boCe?cvid=783ceba35ad741849a60e74acb7763f0


(Bloomberg) -- Amgen Inc. agreed to buy Horizon Therapeutics Plc for about $27.8 billion in its biggest-ever acquisition, deepening its commitment to treatments for autoimmune, inflammatory and rare diseases.

Amgen will pay $116.50 a share in cash, the companies said in a statement Monday, for a premium of about 48% since Horizon Therapeutics disclosed on Nov. 29 that it was in early talks with three suitors. The announcement confirms an earlier report by Bloomberg News.

Horizon shares gained as much as 15% to $112 as of 1 p.m., their highest intraday level since April. Amgen’s fell 1.5%.

Horizon’s therapeutic focus overlaps with that of Amgen, the maker of the Enbrel treatment for autoimmune ailments like psoriasis and ankylosing spondylitis. Such therapies are often tested and used in a wide variety of indications after inititally reaching the market, which can add to sales. Horizon gets almost half its $3.6 billion in annual sales from Tepezza, a treatment for a painful autoimmune condition called thyroid eye disease. In October, Amgen acquired another drug company with a similar immune focus, ChemoCentryx Inc.

Emerging from the exhausting focus on Covid-19, big drugmakers are resuming their search for innovative therapies, especially for those that treat rare diseases and cancer. The deal for Horizon is the biggest in pharma since AstraZeneca Plc bought Alexion Pharmaceuticals for $39 billion in 2020. Horizon is developing drugs for conditions including lupus, alopecia, arthritis and kidney transplant rejection.

Amgen in particular is contending with the threat of diminished revenue as some of its biggest products face the loss of patent protection in the coming years.

“That Amgen is looking for larger deals is not surprising,” given expected erosion of its base business, Wolfe Research analyst Tim Anderson said in a note. “Most often it is companies with future holes to fill that do bigger deals.”

Horizon Therapeutics' acquisition makes a "good strategic and financial sense" for Amgen, says Mizuho's Salim Syed

The deal has the potential to provide a sales boost to Amgen, executives said on a call with investors.

“We’ve admired Horizon’s success for some time and we’ve studied their business closely through time as well,” Amgen Chief Executive Officer Robert Bradway said. “And when presented with this opportunity, we were prepared to move quickly.”

Murdo Gordon, Amgen’s executive vice president for global commercial operations, declined to project potential revenue, citing securities rules in Ireland, where Horizon is based. He said that rapid growth of several of Horizon’s drugs in the US may foreshadow similarly trends in other countries.

“As we secure reimbursement and launch the products in other countries, you can imagine that there’s a lot more growth to generate,” he said.

Sanofi SA dropped out of the running for Horizon Sunday, saying the price had gotten too high, following in the footsteps of a Johnson & Johnson unit earlier this month. The French drugmaker said the “transaction price expectations do not meet our value creation criteria.”

Outperformed Rivals

Thousand Oaks, California-based Amgen has far outperformed those rivals this year, with its stock rising 24% through Friday to a market value of about $149 billion. Amgen last month reported revenue and profit that beat analyst estimates as 11 drugs had record quarterly sales and the company kept operating expenses in check.

Amgen said the purchase of Horizon is expected to increase earnings per share, on a non-GAAP basis, starting in 2024. It anticipates $500 million in annual pre-tax cost savings by the end of the third fiscal year after completion.

Amgen will fund the purchase with a $28.5 billion bridge credit facility from Citigroup Inc. and Bank of America Corp. This is the second time this year the banks have teamed up to advise and fund a large deal, following their work on Philip Morris International Inc.’s purchase of Swedish Match. Amgen had almost $11.5 billion in cash and equivalents at the end of the third quarter.

Horizon, which is traded on the Nasdaq exchange and headquartered in Dublin, has US operations in Deerfield, Illinois, and Rockville, Maryland.

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>>> Axsome Therapeutics Presents New Data from the EVOLVE Open-Label Trial Demonstrating Effects of AUVELITY® on Cognitive and Physical Functioning in Patients with Major Depressive Disorder at the American College of Neuropsychopharmacology (ACNP) 2022 Annual Meeting


GlobalNewsWire

Axsome Therapeutics, Inc.

December 7, 2022


https://finance.yahoo.com/news/axsome-therapeutics-presents-data-evolve-120000447.html


In this article -
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Improvement in cognitive and physical functioning, measured by the CPFQ patient-rated scale, starting at week 1 and sustained over 12 months

Improvement in disability, measured by the SDS, starting at week 1 and sustained over 12 months


NEW YORK, Dec. 07, 2022 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that treatment with AUVELITY® (dextromethorphan HBr-bupropion HCl) resulted in rapid, substantial, and durable improvements in cognitive and physical functioning in the EVOLVE open-label trial in major depressive disorder (MDD). Treatment with AUVELITY also resulted in reduced disability. These new data were presented yesterday at the American College of Neuropsychopharmacology (ACNP) 2022 Annual Meeting being held in Phoenix, Arizona.

In the trial, AUVELITY rapidly, durably, and substantially improved symptoms of depression including cognitive and physical functioning, and reduced disability in patients with MDD who had received one or more prior antidepressants. The change in cognitive and physical functioning was assessed using the Massachusetts General Hospital (MGH) Cognitive and Physical Functioning Questionnaire (CPFQ), a patient-rated scale used to measure cognitive and executive dysfunction in mood and anxiety disorders. The mean CPFQ score at baseline was 28.4. Mean improvements from baseline to weeks 1, 2, and 6 in CPFQ scores were -2.0 points, -4.4 points, and -7.5 points, respectively (p<0.001 for all). Improvements on the CPFQ were sustained through month 6 (-9.5 points, p<0.001) and month 12 (-8.5 points, p<0.001). Disability was assessed using the Sheehan Disability Scale (SDS), a patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The mean SDS score at baseline was 17.5. Mean improvements from baseline to weeks 1, 2, and 6 in SDS scores were -2.9 points, -5.0 points, and -8.3 points, respectively (p<0.001 for all). Improvements on the SDS were sustained through month 6 (-10.1 points, p<0.001) and month 12 (-10.8 points, p<0.001).

EVOLVE (Evaluation of NMDA Modulation for Depressive Episodes) was an open-label, U.S. trial in which 146 patients with MDD who had received one or more prior antidepressants were treated with AUVELITY twice daily for up to 15 months. The primary endpoint was the change from baseline to week 6 on the Montgomery-?sberg Depression Rating Scale (MADRS) total score. Statistical analysis was performed comparing the measures at each timepoint to baseline values as pre-specified (significance level of 0.05, two-sided). AUVELITY was generally well tolerated with long-term treatment and exhibited a safety profile consistent with that observed in previously reported trials. The most common adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), dizziness (5.5%), and insomnia (5.5%).

Details of the poster presentation are as follows:

Title: Improvements in Cognitive and Physical Functioning Outcomes in Depressed Patients Treated with AXS-05 (Dextromethorphan-Bupropion): Results from the EVOLVE Open-label, Long-Term Study

Poster Number: T122
Session: Poster Session II, December 6, 2022

About Major Depressive Disorder (MDD)

Major depressive disorder (MDD) is a debilitating, chronic, biologically-based disorder characterized by low mood, inability to feel pleasure, feelings of guilt and worthlessness, low energy, and other emotional and physical symptoms, and which impairs social, occupational, educational, or other important functioning. In severe cases, MDD can result in suicide. According to the U.S. Department of Health and Human Services, an estimated 21 million U.S. adults experienced MDD each year.1 According to the World Health Organization (WHO), depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease.2 Nearly two-thirds of diagnosed and treated patients do not experience adequate treatment response with available first-line treatment,3 highlighting the need for new therapies.

About AUVELITY®

AUVELITY is a novel, oral, NMDA receptor antagonist with multimodal activity approved for the treatment of MDD in adults. AUVELITY is a proprietary extended-release oral tablet containing dextromethorphan HBr (45 mg) and bupropion HCl (105 mg). The dextromethorphan component of AUVELITY is an antagonist of the NMDA receptor (an ionotropic glutamate receptor) and a sigma-1 receptor agonist. These actions are thought to modulate glutamatergic neurotransmission. The bupropion component of AUVELITY is an aminoketone and CYP2D6 inhibitor which serves to increase and prolong the blood levels of dextromethorphan. The exact mechanism of action of Auvelity in the treatment of depression is unclear. AUVELITY received Breakthrough Therapy designation from the FDA for the treatment of MDD.

INDICATION AND IMPORTANT SAFETY INFORMATION

WHAT IS AUVELITY (aw-VEHL-ah-tee)? It is a prescription oral medicine used to treat adults with major depressive disorder (MDD). It is not known if Auvelity is safe and effective for use in children.
Auvelity is not approved for uses other than the treatment of MDD. The ingredients in Auvelity, bupropion and dextromethorphan, are the same ingredients found in some other medicines approved for other uses.

WHAT IS THE MOST IMPORTANT INFORMATION I SHOULD KNOW ABOUT AUVELITY?

Auvelity and other antidepressant medicines may increase suicidal thoughts and actions in some children, adolescents, and young adults, especially within the first few months of treatment or when the dose is changed. Auvelity is not for use in children.
You should pay close attention to any new or sudden changes in mood, behavior, thoughts, or feelings or if you develop suicidal thoughts or actions. This is very important when starting or changing the dose of an antidepressant medicine.

Call your healthcare provider (HCP) or get emergency help right away if you or your loved one have any of the following symptoms, especially if they are new, worse, or worry you:

suicidal thoughts or actions

new or worsening depression or anxiety

agitation or restlessness

trouble sleeping (insomnia)

acting aggressive, being angry violent

an extreme increase in activity and talking (mania)

panic attacks

new or worsening irritability

acting on dangerous impulses

other unusual changes in behavior or mood

Do not take Auvelity if you:

have or had a seizure disorder.

have or had an eating disorder like anorexia or bulimia.

have recently and suddenly stopped drinking alcohol or use medicines called benzodiazepines, barbiturates, or anti-seizure medicines, and you have recently suddenly stopped taking them.

are taking a monoamine oxidase inhibitor (MAOI), have stopped taking an MAOI in the last 14 days, or are being treated with the antibiotic linezolid or intravenous methylene blue. Ask your HCP or pharmacist if you are unsure whether you take an MAOI. Do not start taking an MAOI until you have stopped taking Auvelity for at least 14 days.

are allergic to dextromethorphan, bupropion, or any other ingredients in Auvelity.

Auvelity may cause serious side effects. Ask your HCP how to recognize the serious side effects below and what to do if you think you have one:

Seizures. There is a risk of seizures during treatment with Auvelity. The risk is higher if you take higher doses of Auvelity, have certain medical problems, or take Auvelity with certain other medicines. Do not take Auvelity with other medicines unless your healthcare provider tells you to.

If you have a seizure during treatment with Auvelity, stop taking Auvelity and call your HCP right away. Do not take Auvelity again if you have a seizure.

Increases in blood pressure (hypertension). Some people may get high blood pressure during treatment with Auvelity. Your HCP should check your blood pressure before you start taking and during treatment with Auvelity.

Manic episodes. Manic episodes may happen in people with bipolar disorder who take Auvelity. Symptoms may include:

greatly increased energy

racing thoughts

unusually grand ideas

talking more or faster than usual

severe trouble sleeping

reckless behavior

excessive happiness or irritability

Unusual thoughts or behaviors. One of the ingredients in Auvelity (bupropion) can cause unusual thoughts or behaviors, including delusions (believing you are someone else), hallucinations (seeing or hearing things that are not there), paranoia (feeling that people are against you), or feeling confused. If this happens to you, call your HCP.

Eye problems (angle-closure glaucoma). Auvelity may cause a type of eye problem called angle-closure glaucoma in people with certain other eye conditions. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are. Call your HCP if you have eye pain, changes in your vision, or swelling or redness in or around the eye.

Dizziness. Auvelity may cause dizziness which may increase your risk for falls.

Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take Auvelity with certain other medicines. Call your HCP or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms:

agitation

hallucinations

confusion

coma

fast heartbeat

blood pressure changes

dizziness

sweating

flushing

high body temperature (hyperthermia)

shaking (tremors), stiff muscles, or muscle twitching

loss of coordination

seizures

nausea, vomiting, diarrhea

COMMON SIDE EFFECTS

The most common side effects of Auvelity include dizziness, headache, diarrhea, feeling sleepy, dry mouth, sexual function problems, and excessive sweating.

These are not all the possible side effects of Auvelity. Tell your doctor if you have any side effects. You can report side effects at 1-800-FDA-1088 or www.fda.gov/medwatch.

BEFORE USING

Tell your HCP about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

It is important to tell your HCP if you are taking:

other medicines containing bupropion or dextromethorphan

medicines to treat depression, anxiety, psychotic or thought disorders, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants

theophylline

corticosteroids

oral diabetes medicines or use insulin to control your blood sugar

medicines to control appetite (anorectic)

nicotine medicines to help you stop smoking

street (illicit) drugs

benzodiazepines, sedative-hypnotic (sleep medicines), or opiates

If you are unsure if you take any of these medicines, ask your HCP. They can tell you if it is safe to take Auvelity with your other medicines.

Tell your HCP if you are pregnant or plan to become pregnant. Auvelity may harm your unborn baby if you take it during pregnancy. Auvelity is not recommended during pregnancy. Your HCP will prescribe another treatment for females who plan to become pregnant.

One of the ingredients in Auvelity passes into your breast milk. Do not breastfeed during treatment with Auvelity and for 5 days after the final dose.

Tell your HCP about all your medical conditions, including if you:

have problems with your liver or kidneys.

have diabetes, heart disease, or high blood pressure.

have a history of seizure, stroke, eating disorder, head injury, or have a tumor in your brain or spinal cord.

have a history of alcohol or drug abuse.

have a history of seizure, eating disorder, or abuse alcohol or drugs.

have low blood sugar, low blood sodium levels, or a history of falls.

you take certain other medicines that could interact with Auvelity.

have or had a condition known as bipolar disorder, a family history of bipolar disorder, suicide, or depression.

have high pressure in the eye (glaucoma).

Review the list below with your HCP. Auvelity may not be right for you if:

you drink a lot of alcohol.

you abuse prescription or street drugs.

you are pregnant or plan to become pregnant.

you are breastfeeding or plan to breastfeed.

HOW TO TAKE

Auvelity is available by prescription only.

Take Auvelity exactly as instructed by your HCP.

Take Auvelity 1 time a day for 3 days, then increase your dose to 2 times a day (taken at least 8 hours apart). Do not take more than 2 Auvelity tablets in 24 hours.

If you miss a dose, do not take an extra dose. Wait and take your next dose at the regular time. Do not take more than 1 dose of Auvelity at a time.

Do not change your dose or stop taking Auvelity without talking to your HCP.

Swallow Auvelity tablets whole. Do not crush, chew, or divide the tablets.

Do not give Auvelity to other people.

If you take too much Auvelity call your HCP or seek medical advice promptly.

LEARN MORE

For more information about Auvelity, call 866-496-2976 or visit Auvelity.com.

This summary provides basic information about Auvelity but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your doctor. Be sure to talk to your doctor or other HCP about Auvelity and how to take it. Your HCP is the best person to help you decide if Auvelity is right for you.

AUV CON BS 10/2022

Please see full Prescribing Information, including Boxed Warning for suicidal thoughts and behaviors, and Medication Guide.

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>>> New data shows Alzheimer's drug can slow cognitive decline


ABC News

by MARY KEKATOS, SONY SALZMAN and FAITH CRITTENDEN

November 29, 2022


https://www.yahoo.com/gma/data-shows-alzheimers-drug-slow-010300428.html


New data shows Alzheimer's drug can slow cognitive decline

In a phase III clinical trial, with results published Tuesday in the New England Journal of Medicine, the drug, Lecanemab -- developed by Eisai and Biogen Inc. -- slowed the rate of cognitive decline by 27% in patients in the early stages of the disease, making it the first drug of its kind to produce such positive trial results, the study showed.

"Lecanemab reduced markers of amyloid in early Alzheimer's disease and resulted in less decline than placebo on all measures of cognition and function at 18 months," said Dr. Christopher Van Dyck, director of the Yale Alzheimer's Disease Research Center, during his presentation of trial efficacy results at the Clinical Trials on Alzheimer's Disease meeting, held in San Francisco.

Researchers followed nearly 1,800 patients over the course of 18 months and found the drug "resulted in moderately less decline on measures of cognition and function," compared to patients who received a placebo.

However, the companies noted that "longer trials are warranted to determine the efficacy and safety of Lecanemab in early Alzheimer's disease."

Patients who have Alzheimer's disease have build-up of two proteins, amyloid-beta and tau, in the brain. They clump together and form plaques, disrupting cell function and causing symptoms such as memory loss and confusion.

Lecanemab is a monoclonal antibody that helps remove the amyloid-beta clumps.

Trial participants were split into two groups, both with a Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score of about 3.2 when the trial began. This score, which measures dementia impairment, has a scale from 0 indicating no impairment to 18.0 indicating severe impairment. A score of 3.2 indicates very mild impairment.

Over the course of 18 months, patients in the Lecanemab group saw their score go up by 1.21 points in comparison with patients in the placebo group, who saw their score go up by 1.66 points.

This is the "most exciting meeting we've had for clinical trials on Alzheimer's disease over the last 10 years (whoopee). I think part of it is that finally we may have a medication that is showing efficacy in this primary outcome of this study," Dr. Babak Tousi, lead Investigator at the Cleveland Clinic study site and an associate professor of neurology and medicine at Lerner College of Medicine at Cleveland Clinic, told ABC News.

It will "not only be able to remove the amyloid plaques on the brain, we were able to show maybe the cognitive decline is less than what's expected without any treatment...So that's the part probably makes it exciting," he added.

There were some adverse events in the trial, the companies said, including about 20% of Lecanemab-treated patients who experienced brain swelling or brain bleeding (yikes), although side effects were largely asymptomatic.

Following the 18-month study, two patients died after experiencing brain hemorrhaging. However, Eisai said no deaths are considered linked to Lecanemab (sure).

Dr. Marwan Sabbah, a neurologist at the Barrow Neurological Institute, said during the presentation Tuesday that doctors will need to proceed with caution when thinking about whether or not to recommend the drug for patients on blood thinners.

The Alzheimer's Association said it was "encouraged" by the news and called on the U.S. Food and Drug Administration to give accelerated approval of Lecanemab. The FDA is currently slated to make an approval decision by Jan. 6, 2023.

If approved, the drug would likely only be given to patients who are in the very early stages of the disease, not to people who already have significant cognitive impairment.

"These peer-reviewed, published results show Lecanemab will provide patients more time to participate in daily life and live independently," the Alzheimer's Association said in a statement. "It could mean many months more of recognizing their spouse, children and grandchildren."

The statement continued, "Treatments that deliver tangible benefits to those living with mild cognitive impairment (MCI) due to Alzheimer's and early Alzheimer's dementia are as valuable as treatments that extend the lives of those with other terminal diseases."

Researchers not involved in the study, including Dr. Leah Croll, a neurologist and assistant professor of neurology at the Lewis Katz School of Medicine at Temple University, said the results were promising.

"This is encouraging news for the millions of Americans affected by Alzheimer's disease, especially because the Alzheimer's drug pipeline has been met with many disappointments over the years," she told ABC News.

There have been hundreds of Alzheimer's drug trials over the years, most with disappointing results.

"Lecanemab is an important incremental change in the way we treat Alzheimer's," Croll said. "I'm hopeful that we are really starting to chip away at this disease process and that in the future, we will have even more options to offer patients."

If the drug gets FDA approval, cost could be a concern. For example, aducanumab, a controversial Alzheimer's drug that was approved last year despite critics arguing that trial data was conflicting, costs about $28,000 per year. (but who cares if it doesn't work and has severe side effects, it's a big money maker for Big Pharma)

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>>> Axsome Therapeutics Announces AXS-05 Achieves Primary Endpoint in the ACCORD Phase 3 Trial in Alzheimer’s Disease Agitation


Axsome Therapeutics, Inc.

November 28, 2022


https://finance.yahoo.com/news/axsome-therapeutics-announces-axs-05-113500324.html


AXS-05 statistically significantly delayed time to relapse of Alzheimer’s disease agitation versus placebo (p=0.014, primary endpoint)

AXS-05 statistically significantly prevented relapse of Alzheimer’s disease agitation versus placebo (p=0.018, key secondary endpoint)

Statistically significant improvement in Alzheimer’s disease agitation, as measured by the CMAI total score, starting at Week 1 with open-label AXS-05 (p<0.001 vs baseline, all timepoints)

Improvement in Alzheimer’s disease agitation, assessed by the modified Alzheimer’s Disease Cooperative Study-CGIC scale, achieved by 66% of patients at 2 weeks and 86% at 5 weeks

Improvement in Alzheimer’s disease agitation, assessed by the PGI-C scale, achieved by 68% of patients at 2 weeks and 89% at 5 weeks

No treatments are currently approved for Alzheimer’s disease agitation


NEW YORK, Nov. 28, 2022 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that AXS-05, a novel, oral, investigational NMDA receptor antagonist with multimodal activity, met the primary and key secondary endpoints in the ACCORD (Assessing Clinical Outcomes in Alzheimer’s Disease Agitation) Phase 3 trial, by substantially and statistically significantly delaying the time to relapse and preventing relapse of agitation in patients with Alzheimer’s disease, as compared to placebo. The ACCORD study was a double-blind, placebo-controlled, multi-center, randomized withdrawal, U.S. trial which treated 178 patients with Alzheimer’s disease agitation. Patients achieving a sustained clinical response after open-label treatment with AXS-05 were randomized (n=108) in a 1:1 ratio to continue treatment with AXS-05 or to discontinue AXS-05 and switch to placebo. AXS-05 has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease agitation. There are currently no FDA-approved treatments for Alzheimer’s disease agitation.

AXS-05 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of agitation symptoms as compared to placebo, with a hazard ratio for time to relapse of 0.275 (p=0.014), representing a 3.6-fold lower risk of relapse compared to placebo. AXS-05 also met the key secondary endpoint of relapse prevention, based on the rates of relapse during the double-blind treatment period (7.5% of AXS-05 patients vs. 25.9% of placebo patients, p=0.018). Relapse was defined as a ≥10-point worsening in the CMAI total score from randomization or a CMAI total score greater than that at study entry; or hospitalization or other institutionalization due to agitation associated with Alzheimer’s disease.

With open-label treatment with AXS-05, patients experienced rapid, substantial, and statistically significant improvement compared to baseline in agitation symptoms. Statistically significant improvement on the Cohen Mansfield Agitation Inventory (CMAI) was seen with open-label AXS-05 treatment at all timepoints starting at Week 1 (p<0.001), with mean reductions from baseline of 11.0 points at Week 2 (p<0.001), and 20.6 points at Week 5 (p<0.001). Improvements were also significant with open-label AXS-05 treatment on all CMAI subscales including the Physically Aggressive subscale at all timepoints (p<0.001).

Jeffrey Cummings, MD, ScD, Director Emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health, and Chambers Professor of Brain Science at the University of Nevada Las Vegas said, “Agitation is one of the most troubling and consequential aspects of Alzheimer’s disease for patients and their caregivers as it is associated with early nursing home placement, accelerated cognitive decline, and increased mortality. The results of the ACCORD trial demonstrate convincing clinical activity for AXS-05 on agitation associated with Alzheimer’s disease based on both a significant delay in symptom relapse as well as a reduction of relapse compared to placebo. Treatment with AXS-05 during the open-label period in a large cohort of patients resulted in rapid and clinically meaningful improvements in Alzheimer’s disease agitation. The improvements were especially notable since they were seen on the aggressive symptom subscales of the agitation measures. Agitation occurs in the majority of patients with Alzheimer’s disease and there are currently no treatments approved for this condition. AXS-05 could potentially fill this high unmet medical need for patients and their caregivers, if approved, based on the observed positive efficacy and favorable safety and tolerability results.”

Rapid and substantial improvement in Alzheimer’s disease agitation was reported by both clinicians and caregivers on global measures. Clinicians reported improvement in agitation in 66.3% of patients at Week 2 and 86.3% at Week 5 after treatment with AXS-05, as assessed using the modified Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change for Agitation (mADCS-CGIC). Caregivers reported improvement in agitation in 67.5% of patients at Week 2 and 89.3% at Week 5 after treatment with AXS-05, as assessed using the Patient Global Impression of Change (PGI-C) rated by the caregiver.

Caregiver distress and burden, patient quality of life, and depressive symptoms were all statistically significantly improved compared to baseline after patients were treated with open-label AXS-05. Caregiver distress was assessed using the NPI Agitation and Aggression Caregiver Distress score (p<0.001, at Weeks 4 and 8). Caregiver burden was assessed using the Zarit Burden Interview (ZBI) (p=0.006 at Week 4, p=0.003 at Week 8). Patient quality of life was assessed using the caregiver rated Quality of Life Alzheimer’s Disease (QoL-AD) scale (p<0.001 at Week 4, p=0.013 at Week 8). Depressive symptoms were assessed using the Cornell Scale for Depression in Dementia (CSDD) (p<0.001, at Weeks 4 and 8).

Herriot Tabuteau, MD, Chief Executive Officer of Axsome said, “With the positive results from ACCORD, AXS-05 has now demonstrated efficacy in the treatment of Alzheimer’s disease agitation in two well-controlled trials. In addition to the strong results versus placebo in the double-blind period, results from the open-label period evidenced rapid, substantial, and significant improvements in Alzheimer’s disease agitation versus baseline with AXS-05 treatment. The ACCORD results complement, and are consistent with, those from the previously completed positive ADVANCE-1 trial. We intend to discuss these findings with the FDA in the context of the ongoing clinical development of AXS-05 in this indication, with the goal of providing a much needed treatment to the millions of patients living with Alzheimer’s disease agitation and their caregivers.”

The rates of adverse events observed in the double-blind period were 28.3% in the AXS-05 group and 22.2% in the placebo group. Discontinuations in the double-blind period due to adverse events were low (0% for AXS-05 and 1.9% for placebo). One serious adverse event was reported in the AXS-05 group (faecaloma), which was determined by the investigator to be not related to study medication, and 2 serious adverse events were reported in the placebo group (cardiac arrest, femur fracture). Falls were reported in 4 patients in the AXS-05 group, none of which were associated with serious adverse events and all of which were determined by the investigators to be not related to study medication, and in 2 patients in the placebo group, one of which was associated with a femur fracture. One death was reported in the placebo group. There was no evidence of cognitive decline for patients treated with AXS-05 as shown by the Mini-Mental State Examination (MMSE), a widely utilized measure of general cognitive function. Treatment with AXS-05 was not associated with sedation.

AXS-05 was granted Breakthrough Therapy designation for the treatment of Alzheimer's disease agitation by the FDA in June 2020. The FDA Breakthrough Therapy designation was supported by the positive results of the ADVANCE-1 trial. A Breakthrough Therapy designation is granted to potentially expedite development and review timelines for a promising investigational medicine when preliminary clinical evidence indicates it may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for a serious or life-threatening condition.

Open-label Period Results Summary

A total of 178 patients were treated with open-label AXS-05 for up to 9 weeks and assessed for efficacy. The primary timepoint for open-label efficacy assessments was 5 weeks, and the key secondary timepoint was 2 weeks. P-values were calculated versus baseline.

The mean CMAI total score was 70.9 at baseline.

Treatment with AXS-05 was associated with a mean reduction from baseline in the CMAI total score of 6.7 points at Week 1, 11.0 points at Week 2, and 20.6 points at Week 5 (p<0.001 for all).

Clinical response on the CMAI (defined as ≥30% reduction from baseline) after treatment with AXS-05 was achieved by 21.8% of patients at Week 1, 40.4% of patients at Week 2, and 70.0% of patients at Week 5.

Treatment with AXS-05 was also associated with improvements on all CMAI subscales including the Physically Aggressive subscale at all timepoints (p<0.001).

Improvement in Alzheimer’s disease agitation, assessed using the clinician rated mADCS-CGIC, was achieved by 47.1% of patients at Week 1, 66.3% of patients at Week 2, and 86.3% of patients at Week 5, after treatment with AXS-05.

Improvement in Alzheimer’s disease agitation, assessed using the caregiver rated PGI-C, was achieved by 51.2% of patients at Week 1, 67.5% of patients at Week 2, and 89.3% of patients at Week 5, after treatment with AXS-05.

Caregiver distress, assessed using the NPI Agitation and Aggression Caregiver Distress score, was significantly reduced after treatment with AXS-05 (p<0.001, at Weeks 4 and 8).

Caregiver burden, assessed using the ZBI, was significantly reduced after treatment with AXS-05 (p=0.006 at Week 4, p=0.003 at Week 8).

Patient quality of life, assessed using the caregiver rated QoL-AD scale, was significantly improved after treatment with AXS-05 (p<0.001 at Week 4, p=0.013 at Week 8).

Depressive symptoms, assessed using the CSDD, were significantly reduced after treatment with AXS-05 (p<0.001, at Weeks 4 and 8).

Double-blind Period Results Summary

A total of 108 patients were randomized, 53 to continued treatment with AXS-05, and 55 switched to placebo. The mean CMAI total scores at randomization were 43.7 and 44.9 for the AXS-05 and placebo groups respectively.

AXS-05 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of Alzheimer’s disease agitation as compared to placebo (hazard ratio for time to relapse of 0.275, p=0.014), demonstrating a 3.6-fold lower risk of relapse compared to placebo.

AXS-05 met the key secondary endpoint by preventing relapse of Alzheimer’s disease agitation as compared to placebo, with 7.5% of AXS-05 patients relapsing versus 25.9% of patients switched to placebo (p=0.018).

The rates of adverse events in the double-blind period were 28.3% in the AXS-05 group and 22.2% in the placebo group. Discontinuations in the double-blind period due to adverse events were low (0% for AXS-05 and 1.9% for placebo).

About the ACCORD Study

ACCORD (Assessing Clinical Outcomes in Alzheimer’s Disease Agitation) was a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate efficacy and safety of AXS-05 in patients with Alzheimer’s disease (AD) agitation. Patients with a diagnosis of probable Alzheimer’s disease and clinically meaningful agitation associated with their disease were enrolled into a 9-week, open-label period, during which they were treated with AXS-05 and monitored for a sustained clinical response. Sustained clinical response was defined as a ≥30% improvement from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) total score and improvement on the PGI-C (score of ≤3) that are both maintained for at least 4 consecutive weeks.

Patients who experienced a sustained clinical response during the open-label treatment period were then randomized in a 1:1 ratio, to continue treatment with AXS-05 or to switch to placebo treatment, in a double-blind fashion for up to 26 weeks. Treatment was continued until either a relapse of agitation symptoms or the end of the 26-week double-blind period, whichever occurred first. Relapse was defined as a ≥10-point worsening in the CMAI total score from randomization or a CMAI total score greater than that at study entry; or hospitalization or other institutionalization due to agitation associated with Alzheimer’s disease.

A total of 178 patients were enrolled into the open-label period and treated with AXS-05, and 108 patients were randomized to continue on AXS-05 (n=53) or to switch to placebo (n=55). The mean Cohen-Mansfield Agitation Inventory (CMAI) total score at baseline study entry was 70.9. The mean CMAI total scores at randomization were 43.7 (AXS-05) and 44.9 (placebo). The minimum score on the CMAI is 29, corresponding to the total absence of symptoms, with higher scores corresponding to greater agitation. The primary endpoint in the study was time from randomization to relapse of Alzheimer’s disease agitation calculated by the Kaplan-Meier estimates and the hazard ratio. The key secondary endpoint, to assess relapse prevention, was the percentage of patients who relapsed. The primary timepoint for open-label efficacy assessments was Week 5 and the key secondary timepoint was Week 2. P-values for the open-label period were calculated versus baseline.

About Alzheimer’s Disease (AD) Agitation

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, and behavioral and psychological symptoms including agitation. AD is the most common form of dementia and afflicts an estimated 6 million individuals in the United States, a number that is anticipated to increase to approximately 14 million by 2050.4 Agitation is reported in up to 70% of patients with AD and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition.1 Agitation in patients with AD has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality.1-3 There are currently no therapies approved by the FDA for the treatment of agitation in patients with AD.

About AXS-05

AXS-05 (dextromethorphan-bupropion) is a novel, oral, patent protected, investigational N-methyl-D-aspartate (NMDA) receptor antagonist with multimodal activity under development for the treatment of Alzheimer’s disease (AD) agitation and other central nervous system (CNS) disorders. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive NMDA receptor antagonist, also known as a glutamate receptor modulator, and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor. AXS-05 is covered by a robust patent estate extending out at least to 2037-2040. AXS-05 was granted FDA Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020. AXS-05 is not approved by the FDA for the treatment of AD agitation.

About Axsome Therapeutics, Inc.

Axsome Therapeutics, Inc. is a biopharmaceutical company developing and delivering novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are committed to developing products that meaningfully improve the lives of patients and provide new therapeutic options for physicians. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.

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>>> Xenon Pharmaceuticals Inc. (XENE), a clinical-stage biopharmaceutical company, engages in developing therapeutics to treat patients with neurological disorders in Canada. Its clinical development pipeline includes XEN496, A Kv7 potassium channel opener that is Phase III clinical trials for the treatment of KCNQ2 developmental and epilepsy encephalopathy; and XEN1101, A Kv7 potassium channel opener, which is in Phase II clinical trial for the treatment of epilepsy and other neurological disorders. The company's product candidates also comprise NBI-921352, a selective Nav1.6 sodium channel inhibitor that is in Phase II clinical trials for the treatment of SCN8A developmental and epileptic encephalopathy, and other potential indications, including adult focal epilepsy; and XEN007, A central nervous system-acting calcium channel modulator, which is in Phase II clinical trials. It has a license and collaboration agreement with the Neurocrine Biosciences, Inc. to develop treatments for epilepsy; and with Flexion Therapeutics, Inc. to develop PCRX301 (XEN402, a Nav1.7 inhibitor) for the treatment of post-operative pain. Xenon Pharmaceuticals Inc. was incorporated in 1996 and is headquartered in Burnaby, Canada.

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>>> Halozyme Therapeutics, Inc. (HALO) operates as a biopharma technology platform company in the United States, Switzerland, Ireland, Belgium, Japan, and internationally. The company's products are based on the ENHANZE drug delivery technology, a patented recombinant human hyaluronidase enzyme (rHuPH20) that enables the subcutaneous delivery of injectable biologics, such as monoclonal antibodies and other therapeutic molecules, as well as small molecules and fluids. Its flagship product is Hylenex recombinant, a formulation of rHuPH20 to facilitate subcutaneous fluid administration for achieving hydration to enhance the dispersion and absorption of other injected drugs in subcutaneous urography and to improve resorption of radiopaque agents.

The company also develops Perjeta; RITUXAN HYCELA and MabThera SC for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL); RITUXAN SC for patients with CLL; and HYQVIA for the treatment of immunodeficiency disorders.

In addition, it is developing Tecentriq for non-small cell lung cancer; OCREVUS for multiple sclerosis; DARZALEX for the treatment of patients with amyloidosis, smoldering myeloma, and multiple myeloma; nivolumab for the treatment of solid tumors; ARGX-113, a human neonatal Fc receptor; ARGX-117 to treat autoimmune diseases; and BMS-986179, an anti-CD-73 antibody.

The company has collaborations with F. Hoffmann-La Roche, Ltd.; Hoffmann-La Roche, Inc.; Baxalta US Inc.; Baxalta GmbH; Pfizer Inc.; Janssen Biotech, Inc.; AbbVie, Inc.; Eli Lilly and Company; Bristol-Myers Squibb Company; Alexion Pharma Holding; ARGENX BVBA; Horizon Therapeutics plc; National Institute of Allergy and Infectious Diseases; Centre for the AIDS Programme of Research in South Africa; and ViiV Healthcare Limited for small and large molecule targets for the treatment and prevention of HIV. Halozyme Therapeutics, Inc. was founded in 1998 and is based in San Diego, California.


https://finance.yahoo.com/quote/HALO/profile?p=HALO


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Veru - >>> Clinical benefit of oral sabizabulin for hospitalized adults with
covid-19 on supplemental oxygen <<<


Sabizabulin - a microtubule disruptor in Phase 3 for prostate cancer. Also has dual anti-viral and anti-inflammatory effects -


Covid 19 trial (204 patients) -- 55% relative reduction in mortality at Day 60, compared to placebo -


https://d1io3yog0oux5.cloudfront.net/_9f49f1321a84e5f1c4b168090b7f711f/verupharma/db/2219/20993/presentation/Veru+Inc+Infectious+Disease+Week+2022+Presentation.pdf



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>>> Why Shares of Veru Fell 10.33% on Monday


Motley Fool

By Jim Halley

Nov 21, 2022


https://www.fool.com/investing/2022/11/21/why-shares-of-veru-fell-1033-on-monday/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article


KEY POINTS

Veru lost $22.2 million in the third quarter.

The stock already lost two-thirds of its value two weeks ago.

Veru is awaiting word from the FDA regarding the status of a drug.


Investors are concerned that approval for a COVID-19 therapy will be delayed or denied.

What happened

Veru (VERU), a biopharmaceutical company that looks for novel cancer therapies, particularly in breast cancer or prostate cancer, saw its shares drop 10.33% on Monday. The stock closed on Friday at $6, then opened on Monday at $5.89. It fell to a low of $5.33 before closing on Monday at $5.38. The stock is down more than 8% so far this year, and has a 52-week high of $24.55 and a 52-week low of $4.34.

So what

The company's stock already lost $10 a share two weeks ago when a Food and Drug Administration (FDA) advisory panel voted 8-5 against approving sabizabulin, Veru's COVID-19 oral therapy, via the Emergency Use Authorization route.

It's not the last word, but the FDA usually agrees with advisory panels' votes. In its discussions regarding the drug, the panel noted the phase 3 trial for sabizabulin had too small a sample size and recommended additional studies before the FDA approved the drug. The company is also expecting the European Medicines Agency's Emergency Task Force review of the drug. Monday's fall reflects continued concerns about the potential FDA decision.

Now what

Veru is struggling financially, so potential bad news regarding sabizabulin is compounded. In the third quarter, the company reported revenue of $9.6 million, down 46% year over year, while it reported a net loss of $22.2 million, or $0.28 in earnings per share (EPS), compared to a net loss in the third quarter of 2021 of $2.7 million, or a loss of $0.03 in EPS.

Veru does have some therapies in late-stage trials, including enobosarm to treat metastatic breast cancer and the combination of enobosarm and abemaciclib, a therapy developed by Eli Lilly (LLY -0.08%) to treat metastatic breast cancer. The FDA granted the combination therapy Fast Track designation.

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>>> Is Axsome Therapeutics Stock a Buy Now?


Motley Fool

By Prosper Junior Bakiny

Nov 11, 2022


https://www.fool.com/investing/2022/11/11/is-axsome-therapeutics-stock-a-buy-now/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article


KEY POINTS

In August, Axsome earned approval for Auvelity, a treatment for major depressive disorder.

Axsome also offers a treatment for excessive daytime sleepiness in narcolepsy patients.

The company's programs target other illnesses where there is an unmet need.

The company seems to be coming into its own.


Axsome Therapeutics (AXSM -0.04%) has had a transformative past 10 months. The biotech company started the year with no drugs on the market, and now its portfolio includes two therapies. That's partly why Axsome stock has crushed the market this year -- although it has been a bit of a roller-coaster ride.

Investors will want to know whether the drugmaker can maintain this momentum. If so, it might be a good idea to consider purchasing its shares today. With that said, let's see what the future may hold for Axsome Therapeutics.

A massive opportunity for Axsome's key asset

In August, Axsome Therapeutics earned approval for Auvelity, a treatment for major depressive disorder (MDD). Before that, in May to be exact, it acquired Sunosi, a treatment for excessive daytime sleepiness in narcolepsy patients, from Jazz Pharmaceuticals. The transaction cost Axsome Therapeutics an upfront payment of $53 million and additional future royalties.

These two medicines will allow the biotech to generate some revenue and help it push other programs through the pipeline. Auvelity, in particular, looks highly promising. It delivered solid results in clinical trials, delivering improvement in depressive symptoms in as fast as two weeks in one phase 3 study, with sustained improvement over a year.

This is in stark contrast to many current options, most of which typically take six to eight weeks to generate results, and that's for those patients for whom they work at all. Initial therapy fails to lead to remission (when the symptoms of the disease decrease or disappear) for 63% of patients. Further, Auvelity's approval comes at an opportune time.

The prevalence of MDD increased during the pandemic, although this trend pre-dates the coronavirus outbreak. Axsome Therapeutics estimates that 8.5% of U.S. adults suffered from symptoms of depression as of 2018, and that number had risen to 27.8% as of April 2020 and again to 32.8% as of one year later. The disease's economic burden is also massive.

In 2018, it was estimated to be $236 billion. With a target market of 19 million people in the U.S., Auvelity could exceed $1 billion in annual sales at its peak in this indication.

More approvals on the way

Axsome Therapeutics is advancing Auvelity in a couple of other indications as well. Most notably, the company could seek approval for this medicine to treat Alzheimer's disease (AD) agitation, a condition marked by aggressive or restless behavior. The company initiated a phase 3 clinical trial for Auvelity in AD in September.

There are about 6 million AD patients in the U.S., 70% of whom suffer from agitation. With an aging population, AD will become even more prevalent, and so will the agitation associated with it. Elsewhere, Axsome is advancing several programs, including AXS-07, a potential migraine treatment. Authorities in the U.S. declined to approve AXS-07 back in May.

Thankfully, the thumbs-down had nothing to do with AXS-07's safety or efficacy. Instead, it was related to manufacturing issues. After talking things through with health industry authorities, Axsome plans to resubmit AXS-07's application in the third quarter of 2023. The company estimates a market of 37 million patients here.

Axsome Therapeutics' other potential targets include smoking cessation, ADHD, fibromyalgia, and cataplexy in narcolepsy patients. Of course, there is no guarantee that everything will go well for the company. It could run into clinical or more regulatory roadblocks, as biotech companies often do. Further, Axsome isn't profitable yet. The company reported $16.8 million in revenue in the third quarter versus none in the prior year.

Axsome Therapeutics' net loss came in at $44.8 million, slightly worse than the $34.9 million net loss reported during the year-ago period. The widening net loss is hardly surprising considering it had to initiate the launch of a brand new product recently. Further, revenue will start coming in more now that Auvelity is approved.

And although the company does run some risks, its market capitalization of $2.5 billion seems more than reasonable given the opportunity of Auvelity in MDD and that of AXS-07 in treating migraines, which is almost certain to hit the market eventually. That's before factoring in the rest of Axsome's pipeline. Given those factors, I still think Axsome Therapeutics is a buy, even after substantially outperforming the market this year.

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>>> Revance Therapeutics, Inc. (RVNC), a biotechnology company, engages in the development, manufacture, and commercialization of neuromodulators for various aesthetic and therapeutic indications in the United States and internationally. The company's lead drug candidate is DaxibotulinumtoxinA for injection, which has completed phase III clinical trials for the treatment of glabellar (frown) lines and cervical dystonia; is in phase II clinical trials to treat upper facial lines, moderate or severe dynamic forehead lines, and moderate or severe lateral canthal lines; and has completed Phase II clinical trials for the treatment of adult upper limb spasticity and plantar fasciitis. It is also developing DaxibotulinumtoxinA in preclinical trial for the treatment of migraine, as well as a topical program for various indications; and OnabotulinumtoxinA, a biosimilar to BOTOX. The company has a collaboration and license agreement with Viatris Inc. to develop, manufacture, and commercialize onabotulinumtoxinA. The company was formerly known as Essentia Biosystems, Inc. and changed its name to Revance Therapeutics, Inc. in April 2005. Revance Therapeutics, Inc. was incorporated in 1999 and is headquartered in Nashville, Tennessee.

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>>> Psychedelic "magic mushroom" drug may ease some depression


AP

by LINDSEY TANNER

November 2, 2022


https://www.yahoo.com/news/psychedelic-magic-mushroom-drug-may-210137044.html


The psychedelic chemical in “magic mushrooms” may ease depression in some hard-to-treat patients, a preliminary study found.

The effects were modest and waned over time but they occurred with a single experimental dose in people who previously had gotten little relief from standard antidepressants.

The study is part of a resurgence of research into potential medical uses of hallucinogenic drugs, and the results echo findings in smaller studies of the mushroom compound psilocybin. The researchers said larger and longer studies are needed to determine the effectiveness and safety of using psilocybin for depression. Their results were published Wednesday in the New England Journal of Medicine.

“The findings are both intriguing and sobering,’’ said Bertha Madras, a psychobiology professor and researcher at Harvard Medical School.

Commenting in a journal editorial, Madras said the study is the most rigorous study to date evaluating psilocybin for treating depression. She was not involved in the research.

Researchers tested the chemical in 233 adults in the U.S., Europe and Canada. Each swallowed capsules containing one of three doses of psilocybin during a 6-to 8-hour session. Two mental health specialists guided them through hallucinatory experiences.

Results for the highest and medium-strength doses were compared with those in the very low dose control group. There was no comparison with an inactive dummy drug or with conventional antidepressants, and there were other limitations.

Depression symptoms declined in all three groups, with the greatest initial improvement in the highest-dose group. At three weeks, 37% of high-dose recipients had substantially improved. But those effects weren’t as good as seen in studies of standard antidepressant drugs, and the results waned in the following weeks.

At three months, 20% in the high-dose group still saw substantial improvement.

Compass Pathways, a London-based firm developing psilocybin for commercial use, paid for and helped conduct the study. It recently announced it is launching a larger, more rigorous study.

Side effects, including headaches and nausea, were common in all three study groups. Serious side effects were uncommon but they included suicidal thoughts and self-injury — mostly in participants with a history of suicidal thoughts.

Dr. David Hellerstein, a co-author and Columbia University research psychiatrist, said those side effects are not surprising given the intensity of the psychedelic experience from the drug. But he said they underscore the importance of using psilocybin in a medical setting.

“This is not a home run, but it’s very encouraging,’’ Hellerstein said, noting that improvement was seen after just one dose.

However, he said it’s likely that additional doses would be needed to achieve long-lasting results. That could make use costly, given the need for several hours of medically supervised treatment.

More than 180 studies of psilocybin and other psychedelics for use in depression, PTSD and other mental conditions are listed on a National Library of Medicine website.

The U.S. government still classifies the chemical as a controlled substance, with no accepted medical use. Several cities have already decriminalized magic mushrooms and Oregon is the first state to approve medical use.

Philip Corlett, an associate psychiatry professor at Yale University, said many important challenges remain, including determining whether psilocybin has any real effect on reducing depression.

One theory is that it stimulates portions of the brain that control levels of the mood-influencing chemical serotonin. It also may reconnect brain circuits — but both theories remain to be proven.

“I think we should be taking our foot off the gas a little bit and figure out exactly how they (psychedelics) work in order to optimize it,’’ Corlett said. “They don’t work for everybody.’’

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>>> Transplant of human brain tissue into rats could help study autism, other disorders

The approach is expected to prompt new research into epilepsy, schizophrenia and intellectual disabilities


Washington Post

By Mark Johnson

October 12, 2022


https://www.washingtonpost.com/science/2022/10/12/brain-tissue-rats-stanford/


Stanford scientists transplanted human brain cells into the brain of a rat. The light flickering on and off shows the human cells as they work inside the brain.

In work that could boost our understanding of brain disorders and enable discovery of new drugs to treat them, researchers at Stanford University School of Medicine transplanted human brain tissue into rats, where it became a functional part of their brains.

Their study, published Wednesday in the journal Nature, took seven years to complete and involved extensive ethical discussions about animal welfare and other issues. The study’s most immediate applications will involve research into conditions such as autism, epilepsy, schizophrenia and intellectual disabilities.

The implanted human brain tissue was created in the lab using a technique that allows scientists to change skin cells into the equivalent of embryonic stem cells — the cells from which all others develop as the embryo grows. In the lab, scientists can nudge these cells down the developmental pathway, growing them into any one of the 200 or so types of cells in the human body.

Researchers created clumps of these cells that resemble parts of the brain. The clumps, known as organoids, resembled the cerebral cortex, the outermost layer of the brain associated with some of its most advanced processes, including language, memory, thought, learning, decision-making, emotion, intelligence and personality.

Using syringes, the scientists injected the human brain tissue into the brains of rat pups two to three days old. Rat brain cells then migrated to the human tissue and formed connections, incorporating the human cells in their brain’s machinery.

“We don’t remove that part of the rat brain. Essentially what happens is that the rat tissue is pushed aside,” said Sergiu Pasca, professor of psychiatry and behavioral sciences at Stanford, who led the study.

The human brain tissue measured roughly one-fifth of an inch when transplanted, but it expanded and by six months accounted for about one-third of the hemisphere of the rat’s brain. The brain is organized into two hemispheres, right and left, each responsible for different functions.

Deep inside the rat’s brain, human and rat cells connected in the thalamus, the area critical for sleep, consciousness, learning, memory and processing information from all of the senses, except for smell.

“Overall, I think this approach is a step forward for the field, and offers a new way to understand disorders” that involve the malfunction of brain cells, said Madeline A. Lancaster, a group leader at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, who did not participate in the study.

“Ethically, there may be concerns about animal welfare, and so just like all animal experimentation, the benefits should always be weighed against the risks to the animal,” Lancaster said. “But I do not have any concerns around whether the human transplants would cause the animal to become more ‘human,’ since the size of these transplants are small and their overall organization is still lacking.”

Pasca said researchers had extensive discussions with ethicists about animal welfare in preparation for the experiments. He said the rats in the study displayed no signs of anxiety, nor was there evidence they suffered pain or seizures.

Japanese stem cell pioneer Yoshiki Sasai is credited with developing the first neural organoid in 2008, but these have had limited impact because they lacked the system of vessels that carries blood throughout the body, Lancaster said. This deficit caused the organoid cells to become stressed and die.

“This study overcomes this limitation by transplanting organoids into the rat brain where the organoids can become vascularised,” Lancaster said. “The result is much more mature” structures, connections and activity from the transplanted tissue inside the rat.

In one experiment, the Stanford team took skin cells from a person with a rare genetic condition called Timothy syndrome, which has some of the characteristics of autism and epilepsy and has been diagnosed in fewer than 100 people worldwide. Using the ability to change skin cells into other types of cells, researchers created brain organoids from the patient and implanted them into one side of the rat’s brain.

For comparison, they transplanted organoids from a healthy person into the other side of the same rat’s brain. They discovered that after five to six months, the Timothy syndrome cells were smaller and involved in very different electrical activity than the healthy brain cells.

“I’m not entirely surprised by the findings, but it’s super cool,” said Bennett Novitch, a member of the Broad Center of Regenerative Medicine and Stem Cell Research at the University of California at Los Angeles, who was not involved in the study. In 2021, Novitch and colleagues developed organoids that produced brain waves, the electrical pulses that brain cells use to communicate with one another.

He said the Stanford scientists showed that human brain organoids could not only be integrated into the rat brain, but also used to change the animal’s behavior.

In a complex experiment, they created clumps of human brain cells that had been customized so that individual neurons could be switched on by a specific frequency of blue laser light. Those clumps were then injected into rat brains, and after three months the scientists threaded ultrathin fiber-optic cables into the rat brains so the researchers could beam in blue light.

The rats were placed in glass boxes with a water spout. The researchers then conditioned the rats to expect water only after their brains had received a pulse of blue light. The rats grew to associate the blue light with receiving water, showing that the implanted human cells were now involved in the complex reward-seeking machinery inside their brains.

“This is very difficult experimentation to do,” Novitch said.

He noted, however, that using rats implanted with human brain tissue for testing drugs would work for small studies but not for pharmaceutical companies because of the speed and scale required.

Pasca said he hopes to teach other researchers to use his group’s techniques to study different brain disorders.

“There are enough problems in neuroscience to solve to last for many years to come,” he said. “The challenge of understanding psychiatric disorders is immense.”

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JSPR Jasper Therapeutics Announces Positive Clinical Data from Investigator Sponsored Study of JSP191 Conditioning in Fanconi Anemia Patients at IEWP Annual Meeting

Jasper Therapeutics
Mon, September 26, 2022 at 8:00 AM

Pincher chart as well.

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>>> Evolus, Inc. (EOLS), a performance beauty company, provides medical aesthetic products for physicians and their patients in the United States. It offers Jeuveau, a proprietary 900 kilodalton purified botulinum toxin type A formulation for the temporary improvement in the appearance of moderate to severe glabellar lines in adults. The company was incorporated in 2012 and is headquartered in Newport Beach, California.

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>>> Arbutus Biopharma Corporation (ABUS), a biopharmaceutical company, develops novel therapeutics for chronic Hepatitis B virus (HBV) infection, SARS-CoV-2, and other coronaviruses in the United States.

Its HBV product pipeline consists of AB-729, a proprietary subcutaneously delivered RNA interference product candidate, which in Phase Ia/Ib clinical trial targeted to hepatocytes that inhibits viral replication and reduces various HBV antigens using novel covalently conjugated N-acetylgalactosamine (GalNAc) delivery technology; and AB-836, an oral capsid inhibitor that suppresses HBV DNA replication.

The company's research and development programs include AB-161, an oral HBV RNA destabilizer to destabilize HBV RNA, which leads in the reduction of HBsAg and other viral proteins; AB-101, an oral PD-L1 inhibitor to reawaken patients' HBV-specific immune response; and small molecule antiviral medicines to treat coronaviruses, including COVID-19.

It has strategic alliance, licensing, and research collaboration agreements with Talon Therapeutics, Inc.; Gritstone Oncology, Inc.; Alnylam Pharmaceuticals, Inc.; Qilu Pharmaceuticals Co, Ltd.; Assembly Biosciences, Inc.; Acuitas Therapeutics, Inc.; and Antios Therapeutics, Inc. Arbutus Biopharma Corporation also has a clinical collaboration agreement with Vaccitech plc to evaluate a triple combination of AB-729 for the treatment of chronic HBV infection. The company was formerly known as Tekmira Pharmaceuticals Corporation and changed its name to Arbutus Biopharma Corporation in July 2015. Arbutus Biopharma Corporation is headquartered in Warminster, Pennsylvania.

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https://finance.yahoo.com/quote/ABUS/profile?p=ABUS


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>>> Revance Announces Proposed Public Offering of Common Stock


BusinessWire

September 12, 2022


https://finance.yahoo.com/news/revance-announces-proposed-public-offering-200100718.html


NASHVILLE, Tenn., September 12, 2022--(BUSINESS WIRE)--Revance Therapeutics, Inc. (Nasdaq: RVNC), a commercial stage biotechnology company focused on innovative aesthetic and therapeutic offerings ("Revance" or the "Company"), today announced a proposed underwritten public offering of $150 million of its common stock. In addition, Revance expects to grant the underwriters a 30-day option to purchase up to an additional 15% of the shares of its common stock offered in the offering. The Company intends to use the net proceeds from the offering to fund the commercialization of DAXXIFY™, the RHA® Collection of dermal fillers and OPUL®, and for working capital, research and development and general corporate purposes. The offering is subject to prevailing market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

Goldman Sachs & Co. LLC, Cowen and Company, LLC and Guggenheim Securities, LLC are acting as joint book-running managers for the proposed offering. Barclays Capital Inc. is also acting as a bookrunner for the proposed offering.

The securities described above are being offered by Revance pursuant to an automatic shelf registration statement on Form S-3 (File No. 333-250998) previously filed with the Securities and Exchange Commission on November 27, 2020. The offering will be made only by means of a prospectus supplement. When available, copies of the preliminary prospectus supplement and accompanying prospectus relating to the proposed public offering may be obtained by contacting Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at 1-866-471-2526, or by email at [e-mail]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by telephone at [phone], or by email at [e-mail]; Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, New York 10017, or by telephone at [phone], or by email at [e-mail]; or Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by telephone at [phone], or by email at [e-mail].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

About Revance

Revance is a commercial stage biotechnology company focused on developing and commercializing innovative aesthetic and therapeutic offerings, including DAXXIFY™ (DaxibotulinumtoxinA-lanm) for injection, the RHA® Collection of dermal fillers, and OPUL®, a relational commerce platform for aesthetic practices. Revance has also partnered with Viatris Inc. to develop a biosimilar to BOTOX®, which would compete in the existing short-acting neuromodulator marketplace. Revance’s therapeutics pipeline is currently focused on muscle movement disorders including evaluating DaxibotulinumtoxinA for Injection in cervical dystonia and upper limb spasticity.

Revance, the Revance logo and OPUL® are registered trademarks of Revance Therapeutics, Inc.

Resilient Hyaluronic Acid® and RHA® are registered trademarks of Teoxane SA.

BOTOX® is a registered trademark of Allergan, Inc.

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Blade, Thanks for the CRDF info. Just curious about other bio stocks you are currently following? Thanks.

Revance looks like a long term winner after the recent FDA approval, and the stock has largely been 'de-risked'.

Axsome also has a recent FDA approval. Dew didn't seem too interested in AXSM's program since it's a combo version of two already approved drugs, but it's rapid onset makes it unique among antidepressants, and the NMDA mechanism is also different. NMDA also entered the picture with the ketamine isomer Spravato, which was approved several years ago. Fwiw, from the Cortex days, I remember AMPA and NMDA being the two main glutamate receptors, so even though AMPA largely flopped, it's nice to see NMDA having some success :o)




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CRDF presentations at ESMO


Cardiff Oncology Announces New Preclinical and Clinical Data from Program in KRAS-mutated Metastatic Colorectal Cancer (mCRC) at the ESMO Congress 2022
Sat, September 10, 2022 at 4:30 AM


CRDF
+0.69%

Durable responses to treatment, with a median duration of response (mDoR) of 11.7 months, reported in Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC

Observed mDoR is supported by preclinical findings that demonstrate onvansertib in combination with irinotecan can overcome intrinsic and refractory resistance to irinotecan in patient-derived xenograft models

Patients with a ≥90% decrease in KRAS mutant allele frequency (MAF), a response biomarker, in the first cycle of treatment had significantly higher ORR and longer PFS in Phase 1b/2 trial and an Expanded Access Program (EAP)

SAN DIEGO, Sept. 10, 2022 /PRNewswire/ -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced new preclinical and clinical data from its program in KRAS-mutated mCRC. The data are featured in two posters being presented at the European Society for Medical Oncology (ESMO) Congress 2022, which is taking place at the Paris Expo Porte de Versailles in Paris, France, and virtually.

Cardiff Oncology is a clinical-stage biotechnology company and our mission is to develop new treatment options for cancer patients in indications with the greatest medical need. Our goal is to overcome resistance, improve response to treatment and increase overall survival. Our investigational drug, onvansertib, a first-in-class, third-generation Polo-like Kinase 1 (PLK1) inhibitor, is being evaluated in combination with standard-of-care chemotherapy and targeted therapeutics. We are assessing tumor genomics and using our expertise in biomarker technology to rapidly evaluate patient response to treatment. (PRNewsfoto/Cardiff Oncology, Inc.)
Cardiff Oncology is a clinical-stage biotechnology company and our mission is to develop new treatment options for cancer patients in indications with the greatest medical need. Our goal is to overcome resistance, improve response to treatment and increase overall survival. Our investigational drug, onvansertib, a first-in-class, third-generation Polo-like Kinase 1 (PLK1) inhibitor, is being evaluated in combination with standard-of-care chemotherapy and targeted therapeutics. We are assessing tumor genomics and using our expertise in biomarker technology to rapidly evaluate patient response to treatment. (PRNewsfoto/Cardiff Oncology, Inc.)
More
Poster 397P: Early Decreases in KRAS Mutant Allele Frequency (MAF) Predict Clinical Benefit to the PLK1 Inhibitor Onvansertib in Combination with FOLFIRI/bev in 2L Treatment of Metastatic Colorectal Carcinoma (mCRC)

Poster 397P includes updated data (data cut-off date: July 25, 2022), as well as the results of correlative biomarker analyses from a Phase 1b/2 clinical trial of onvansertib plus FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC. Measures of clinical response were compared between subsets of patients defined as KRAS responders or non-responders. KRAS responders were defined as patients with a ≥90% decrease in KRAS mutant allele frequency (MAF) in circulating tumor DNA (ctDNA) after one treatment cycle.

"The data from this trial show onvansertib plus FOLFIRI and bevacizumab outperforming historical controls on multiple key endpoints and are highly encouraging," said Heinz-Josef Lenz, MD, FACP, professor of medicine at USC Norris Comprehensive Cancer Center and the trial's principal investigator. "They suggest trial participants with various KRAS mutations experience durable clinical benefits and that the onvansertib-FOLFIRI combination is avoiding the mechanisms that typically drive rapid acquired resistance to the standard-of-care (SoC). This highlights onvansertib's potential to fill a crucial gap in mCRC's therapeutic paradigm, as there are currently limited options available for second line patients. In addition, the significant increases between response rates and progression-free survival in KRAS responders point to changes in MAF as a potential blood-based biomarker that could aid in treatment decisions."

Key data and conclusions presented in the poster include:

Overall response rate (ORR) and median progression-free survival (mPFS) reported in Phase 1b/2 trial substantially exceed those reported in historical control trials

ORR across all evaluable patients was 35%, with 17 of 48 evaluable patients achieving an objective response and responses have been observed across multiple KRAS variants

Median duration of response (mDoR) across all evaluable patients was 11.7 months (95% confidence interval (CI): 8.9 – not reached)

mPFS across all evaluable patients was 9.3 months (95% CI: 7.6 – 13.5)

Historical control trials of different drug combinations, including the standard-of-care (SOC) of FOLFIRI with bevacizumab, in similar patient populations have shown ORR and mPFS of 5 – 13% and ~4.5 – 5.7 months, respectively1-4

KRAS responders showed significantly greater ORR and mPFS compared to non-responders

ORR in KRAS responders vs. KRAS non-responders: 63.6% (14/22) vs. 8.7% (2/23) (p = 0.00014)

mPFS in KRAS responders vs. KRAS non-responders: 12.6 months vs. 6.0 months (p=0.019)

Poster 366P: The PLK1 Inhibitor Onvansertib Overcomes Irinotecan Resistance in RAS-mutated Metastatic Colorectal Cancer (mCRC) In Vivo and in Patients

Poster 366P includes findings (as of August 5, 2022) from Cardiff Oncology's EAP of onvansertib in KRAS-mutated mCRC, as well as data from murine studies evaluating onvansertib in combination with irinotecan in 6 PDX models of irinotecan-resistant, RAS-mutated CRC. Clinical findings reported in the Expanded Access Program (EAP) were compared between KRAS responders and non-responders. To enroll in the EAP, a patient must have been ineligible for the Phase 1b/2 clinical trial having received prior treatment with irinotecan or failed or progressed on multiple prior lines of standard-of-care therapy. EAP patients are treated with the same treatment regimen (onvansertib 15 mg/m2 plus FOLFIRI and bevacizumab) and dosing schedule as patients in the Phase 1b/2 clinical trial.

Scott Kopetz, MD, PhD, FACP, professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center commented, "Currently available third-line or later treatment options for patients are severely limited, due in large part to the high prevalence of tumors that show resistance to irinotecan. Based on the findings being presented at ESMO, combining onvansertib with the current SOC appears to be an innovative strategy that can overcome irinotecan resistance and address a broad and pressing unmet need. This hypothesis is further supported by onvansertib's mechanism of action, which targets DNA damage repair pathways underlying resistance to irinotecan and other chemotherapeutic agents."

Key findings and conclusions presented in the poster include:

EAP patients with prior irinotecan treatment (43 out of a total of 51 EAP patients) showed clinical benefit following treatment with onvansertib plus FOLFIRI/bevacizumab

mPFS was 4.04 months (95% CI: 2.96 – 8.38); 6-month PFS rate was 37.3% (95% CI: 24.9 – 55.8)

Of EAP patients with prior irinotecan treatment, KRAS responders had significantly longer PFS compared to non-responders.

mPFS in KRAS responders vs. KRAS non-responders: 11.18 months vs. 3.25 months (p=0.0014)

The combination of onvansertib and irinotecan showed significantly greater anti-tumor activity compared to onvansertib monotherapy in 5 of 6 tested PDX models of irinotecan-resistant, RAS-mutated CRC.

The ESMO posters are currently available for viewing on the congress's virtual platform and will also be presented by Drs. Lenz and Kopetz during Poster Sessions 8 and 7, respectively, on September 11, 2022. Following the congress, the posters will be available on the "Scientific Presentations" section of the Cardiff Oncology website at https://cardiffoncology.com/scientific-presentations/.

Clinical and Corporate Update Conference Call and Webcast
Cardiff Oncology will host a webcast and conference call to provide a clinical and corporate update to the investment community on Monday, September 12, 2022 at 4:30 PM ET. The event will feature discussions on the planned development pathway for onvansertib in KRAS-mutated metastatic colorectal cancer and updates on other development programs. In addition, company management will provide data updates from ongoing clinical trials. To access the call, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13731618. The conference call will also be webcast live and a link to the webcast can be accessed here. A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.

About the Phase 1b/2 Trial of Onvansertib in the Second-Line Treatment of KRAS-mutated mCRC
This is a multi-center, single-arm, Phase 1b/2 trial of onvansertib in combination with standard-of-care FOLFIRI and Avastin® (bevacizumab) to evaluate the safety and preliminary efficacy of the combination regimen in the second-line treatment of patients with KRAS-mutated mCRC. The trial, A Phase 1b/2 Study of Onvansertib (PCM-075) in Combination with FOLFIRI and Bevacizumab for Second–Line Treatment of Metastatic Colorectal Cancer in Patients with a KRAS Mutation, is enrolling patients with histologically confirmed metastatic and unresectable colorectal carcinoma harboring a KRAS mutation. Patients must also have experienced disease progression or treatment intolerance to first-line treatment with fluoropyrimidine and oxaliplatin (FOLFOX or CapeOx) with or without bevacizumab to be eligible. The trial is being conducted at the following cancer centers across the U.S.: USC Norris Comprehensive Cancer Center, The Mayo Clinic (Arizona, Rochester, and Jacksonville), Kansas University Medical Center (KUMC), CARTI Cancer Center and Inova Schar Cancer Institute. For more information on the trial, please visit NCT03829410.

About the EAP for Onvansertib in KRAS-mutated mCRC
Sometimes called "compassionate use", expanded access is a potential pathway for a patient with a serious or life-threatening disease to gain access to an investigational drug for treatment outside of a clinical trial, particularly when no comparable or satisfactory alternative therapy options are available. The Cardiff Oncology EAP in KRAS-mutated mCRC is using the same combination treatment regimen (onvansertib 15 mg/m2 + FOLFIRI and bevacizumab) and dosing schedule as the ongoing Phase 1b/2 clinical trial and is intended for patients that have progressed on prior therapy and do not meet the second line eligibility criteria for enrollment in the clinical trial. The program has reached capacity and is no longer open to enrollment.

References:

Giessen et al., Acta Oncologica 2015, 54: 187-193
Cremolini et al., Lancet Oncol 2020, 21: 497–507
Antoniotti et al., Correspondence Lancet Oncol June 2020
Bennouna et al., Lancet Oncol 2013; 14: 29–37
About Cardiff Oncology, Inc.
Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers. Our lead asset is onvansertib, a PLK1 inhibitor we are evaluating in combination with standard-of-care (SOC) therapeutics in clinical programs targeting indications such as KRAS-mutated metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma, and metastatic castrate-resistant prostate cancer. These programs and our broader development strategy are designed to target tumor vulnerabilities in order to overcome treatment resistance and deliver superior clinical benefit compared to the SOC. For more information, please visit https://www.cardiffoncology.com.


Bladerunner

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Revance - >>> FDA Approves New Botox Competitor From Revance Therapeutics


Barron's

By Josh Nathan-Kazis

Sept. 8, 2022


https://www.barrons.com/articles/botox-daxxify-revance-therapeutics-stock-51662647662?siteid=yhoof2


The Food and Drug Administration on Thursday approved a new competitor to the anti-wrinkle injection Botox. Analysts have said it could be the first new entrant to disrupt Botox’s market dominance.

The new drug, called Daxxify, represents the first approval for biotech Revance Therapeutics (ticker: RVNC). Revance stock is up 12.2% on Thursday to $23.31, and its year-to-date gain stands at 43.1%.

Shares of AbbVie (ABBV), which has sold Botox since its $63 billion buyout of Allergan in 2020, are up 0.4% on Thursday.

The FDA approved Daxxify to temporarily improve moderate to severe frown lines in adults. The drug has shown to have a longer duration of effect than its competitors, with a median duration of six months. That could give the drug a chance to make a dent in Botox’s position, where other new entrants to the market, like Evolus ‘ (EOLS) Jeuveau, have struggled.

In a note out in April, Cowen analyst Ken Cacciatore wrote that his survey of experts showed that Daxxify’s durability of effect, and its product profile, will “lead to disruption.” He said that his experts believe that 30% of their patients taking injections of Daxxify’s type would be receiving Daxxify within the next three years, rather than competitors such as Botox.

Cacciatore wrote that sales of Daxxify could eventually top $1 billion per year. AbbVie reported Botox sales of $2.2 billion in 2021.

In a separate note in May, Piper Sandler analyst David Amsellem wrote that total sales for U.S. Revance “well north of $500M+” per year are “realistic.” Revance sales were $77.8 million last year. The FactSet analyst consensus estimate has total Revance sales rising to $203.4 million in 2023, and $876.8 million in 2027.

“Daxxify is setting the new standard for neuromodulator formulation,” Revance CEO Mark Foley said on an investor call on Thursday morning. “The neuromodulator market has remained largely unchanged for over 30 years and is ripe for innovation. While new products have entered the market, they all have similar formulations and performance profiles, delivering a median duration of effect of 12 to 16 weeks.”

Revance’s president, Dustin Sjuts, said that the company would roll the drug out slowly, beginning with a preview program for some doctors, and then moving on to a broader commercial launch next year.

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>>> After a lengthy drought, could biotech M&A be on the upswing?

The second quarter was one of the busiest three-month periods for acquisitions in recent years. Some industry watchers expect that pace to continue.


Pharmadive

July 8, 2022

Jacob Bell


https://www.biopharmadive.com/news/biopharma-deals-mergers-acquisitions-2022-first-half/626798/


Mergers and acquisitions in the pharmaceutical industry were more abundant in the second quarter than during the same period in years’ past, an uptick in activity that could help the sector rebound from a historic downturn.

Between April and June, there were at least 14 biopharma acquisitions worth $50 million or more, a tally roughly two- to three-times larger than what was seen in that stretch in each of the last four years. And if megadeals like AbbVie’s 2019 takeover of Allergan weren’t factored in, this year’s second quarter would outrank the prior four in value, with approximately $23.4 billion spent on buyouts.

Almost half of that sum came from Pfizer’s $11.6 billion purchase of Biohaven Pharmaceuticals, the neuroscience-focused company that sells the migraine medication Nurtec ODT. But three other acquisitions also surpassed the billion-dollar mark, and involved smaller makers of vaccines and cancer drugs getting absorbed by much larger, multinational firms like Bristol Myers Squibb and GlaxoSmithKline.

This uptick comes after a somewhat prolonged dearth of dealmaking. In a January report, financial services firm Ernst & Young found that 2021 was one of the least active years for biopharma M&A in the last decade. At $108 billion, last year’s cumulative deal value was lower than the $128 billion recorded in 2020 and less than half the $261 billion seen in 2019, according to EY.

To some industry followers, the number and size of recent transactions may not be so surprising. Last year, analysts at the investment bank SVB Securities wrote that they expected the pace of biopharma dealmaking to either hold or increase in 2022.

Such predictions have hinged on several factors, with one being the amount of cash many would-be acquirers are sitting on. Pfizer, thanks in part to its coronavirus vaccine, ended the first quarter with $2.5 billion in cash and cash equivalents and another $21.4 billion in short-term investments. Swiss pharmaceutical giant Novartis, meanwhile, just sold off billions of dollars worth of stock in crosstown rival Roche.

Merck, maker of the COVID-19 pill Lagevrio and the blockbuster cancer therapy Keytruda, also had nearly $8.6 billion in cash and cash equivalents by the end of March. Merck may be looking to put that money to work, too, as The Wall Street Journal reported last month, and again Thursday, that the company could acquire Seagen, a Seattle-based cancer drugmaker currently worth more than $32 billion.

While Seagen’s share price has grown since the buyout talks became public, a broad downturn in the biotech stock market has deflated the valuations of many younger, smaller drug companies. Now, amid concerns that funding may be harder to come by, dozens of biotechs are reorganizing or shedding programs to save cash. In a June report, accounting firm PwC noted that more than 60 have announced layoffs this year, with several ending operations altogether.

Private biotechs are facing a tougher environment too, with venture financing numbers trending downward and little demand for initial public offerings.

But another effect of lower valuations, according to deal experts, could be more M&A. “With capital becoming harder to come by for most biotechs, pharma is in a good position to acquire many of these companies at a discount from their highs of just a couple years ago,” partners at PwC wrote in the report.

Throughout 2019 and 2020, biopharma buyers often paid at least double the market value of the companies they were acquiring. And though premiums have remained in the triple-digits for some deals this year, others like the Pfizer-Biohaven one or GSK’s purchase of Sierra Oncology fell in the range of about 40% to 80%. In some cases, like the buyouts of Radius Health and Epizyme, biotechs have sold themselves for prices at or near all-time lows.

Such deals suggest that while biotech executives “have been slow to accept lower valuations … more companies are willing to explore alternative means of financing as capital becomes harder to come by,” the PwC partners wrote.

If the recent deal spree continues, it may provide a boost to the biotech industry. M&A is one of the main ways investors gauge the health of the sector and their ability to secure returns, so increased activity could reinstill confidence.

Looking ahead, the PwC partners expect dealmaking to continue. They believe large pharmaceutical companies will pursue acquisitions to, among other reasons, bring in new drugs that can help offset the expected losses should some of their key products lose patent protection over the next several years.

“All of the stars are aligned for there to be a flurry of deals activity across all areas of the sector,” the partners wrote.

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Blade, Looks like a lot of bargains in bio-land right now -


ChemoCentryx - >>> How Covid, 'industrial logic' and a threat played out in a multibillion-dollar biotech merger



By Ron Leuty

San Francisco Business Times

Sep 1, 2022


https://www.bizjournals.com/sanfrancisco/news/2022/09/01/amgen-chemocentryx-amgn-ccxi-tavneos-merger-buyout.html?utm_source=sy&utm_medium=nsyp&utm_campaign=yh


Amgen Inc.'s persistence and patience won out in a 29-month saga that landed it a Peninsula company with a potential $2 billion-a-year drug for an inflammatory blood vessel disease.

The $3.7 billion merger between Amgen and ChemoCentryx Inc., outlined in a Securities and Exchange Commission proxy filing Wednesday, stretched across the early days of the Covid-19 pandemic, the first drug approval in ChemoCentryx's 25-year history and a threat by one bidder to go directly to shareholders to win approval for an offer that proved $8-per-share less than that tendered by Amgen.

In the end, though, the filing painted ChemoCentryx founder, Chairman, President and CEO Tom Schall and his board as a jar of cool cucumbers, balancing a vastly superior offer from Amgen against the potential of getting a better price.

The story begins with the board of ChemoCentryx (NASDAQ: CCXI), senior management and its counsel, Latham & Watkins LLC, talking on March 3, 2020, about the company's then-upcoming request that the Food and Drug Administration approve the drug avacopan for patients with ANCA-associated vasculitis. The disease leads to destruction of blood vessels when the immune system mistakenly attacks them, setting off a progressive decline leading to end-stage kidney disease.

At an executive session after the meeting, Schall and board members discussed whether ChemoCentryx should consider some kind of partnership, equity financing or a broader transaction. They decided it would be "appropriate" for Schall and his management team to make introductory calls to investment bankers that could assist in a potential deal.

That set off a process where financial advisor Goldman Sachs contacted 13 potential parties. Five of those companies, including Amgen (NASDAQ: AMGN), through early June 2020 got presentations from ChemoCentryx management about the company and its drug pipeline.

But generalist investors, propelled by early movement toward Covid vaccines and Gilead Sciences Inc.'s Covid treatment remdesivir, flooded the biopharma market and pushed the price of ChemoCentryx's stock from $38.96 per share in early April to nearly $61 on June 1. Goldman Sachs said "several" companies were interested in ChemoCentryx but said an acquisition would be "challenging" with amped up bipharma valuations.

ChemoCentryx's board — a group including former executives of former Abbott Laboratories executive vice president James Tyree, former Pfizer Inc. chief medical officer Dr. Joseph Feczko, retired AstraZeneca plc executive Dr. David Wheadon and retired Latham & Watkins partner Thomas Edwards — instead pushed senior management to pursue a public offering.

In the meantime, however, a company identified only as "Party D" reached out to Goldman Sachs by phone about "a potential path forward" for an acquisition. Still, within four days, the company had decided not to pursue buying ChemoCentryx.

ChemoCentryx, which had reported cash, equivalents, restricted cash and investments as of March 31 totaling about $190 million, then netted an additional $282.9 million by selling 5.2 million shares.

And it continued on its plan to stand alone.

For the next 16 months, that's how things stood, until the FDA on Oct. 8, 2021, approved avacopan, now branded as Tavneos. A week later, Amgen's senior vice president of business development, Rachna Khosla, called Markus Cappel, ChemoCentryx's chief business officer, to congratulate him on Tavneos' approval. The next month, Khosla asked about ChemoCentryx's plans for commercializing Tavneos and suggested that Schall and Amgen Chairman, President and CEO Robert Bradway meet.

Schall and Bradway talked over the phone for the first time last Dec. 7 — the first of many conversations between the executives. They and other executives met in-person in mid-January at ChemoCentry's San Carlos headquarters on the final day of the J.P. Morgan Healthcare Conference — 25 miles to the north in San Francisco — to talk about ChemoCentryx pipeline and progress with the launch of Tavneos.

ChemoCentryx leaders told Amgen officials they were "not interested in program-by-program business development discussions" — in other words, Amgen had to want all of ChemoCentryx: Tavneos, pipeline and all. As the meeting closed, Amgen officials invited ChemoCentryx representatives to a followup meeting at their headquarters in southern California's Thousand Oaks.

By late February, after a series of meetings, Bradway told Schall he was prepared to talk to Amgen's board about an acquisition of ChemoCentryx. But Bradway had one request of Schall: Give me a number, some kind of valuation range.

Schall, who stands to make $20.2 million in cash, equity and bonuses if the deal is approved by ChemoCentryx shareholders in the fourth quarter, played coy. He stressed the company's pipeline, including its oral cancer immunology drug CCX-559.

At the time, ChemoCentryx's stock price, like many in the biotech industry, had been nearly halved from the previous June, closing Feb. 25 at $30.63 per share.

By March 3, Bradway delivered to Schall a "preliminary indication of interest" at $42.50 per share, representing a 74% premium from the $24.42 price ChemoCentryx's stock closed that day.

A few days later, on March 7, ChemoCentryx's board determined the offer undervalued the company and directed Schall to decline it and not engage in any valuation discussions unless Amgen "meaningfully increased" its proposal.

By March 18, ChemoCentryx's board had re-engaged Goldman Sachs to look anew at the marketplace and ChemoCentryx's prospects for going it alone with Tavneos now on the market.

But by April 25, Khosla had reached out to Cappel again, and the next day she said Amgen's senior management continued to be interested in ChemoCentryx, Tavenos and its "belief in the industrial logic of a potential big transaction" between the companies.

By mid-May, Bradway was back on the phone with Schall, asking for guidance again on a price that would put Amgen in the ballpark to acquire ChemoCentryx. PJT Partners LP, Amgen's financial advisor, reached out to Goldman Sachs with the same request for guidance. By May 20, Goldman Sachs had an answer: Think of something above $50 per share.

Bradway and Schall would talk three more times in the first half of June, with Bradway saying he "needed assistance" on some questions before Amgen could increase its offer. Finally, on June 23, Bradway said Amgen could pay $51 per share.

ChemoCentryx's stock that day closed at $22.17.

With information from Goldman Sachs, ChemoCentryx's board the next day told senior management to stay engaged with Amgen but see if the diligence process could entice the 24,000-employee biotech, which has research and development operations in South San Francisco, to boost its offer for 180-employee ChemoCentryx.

But on July 12, the CEO of a drug developer known in the SEC filing as "Party E" called Schall. The company the next day made a $36-per-share offer for ChemoCentryx; Schall said his personal view was that the offer "would not be sufficient," and by July 19, "Party E" had boosted its offer to $40.

The next day, ChemoCentryx's board directed Goldman Sachs to reach out to four other "global biopharmaceutical companies" — three of which it had contacted back in spring 2020, including the once-interested "Party D," as well as a potential new player.

Meanwhile, representatives of "Party E," told by Schall July 21 that the $40 offer was "inadequate" and by Goldman Sachs that they needed to come back with something above $50, said their company "may need to move in a different direction."

The CEO of "Party E" laid out that direction to Schall the next week, saying ChemoCentryx stockholders would find the $40 offer "compelling." The suitor was willing to negotiate in private, the CEO said, according to the SEC filing, "but noted that he was prepared to present (the) proposal publicly to ChemoCentryx shareholders."

Schall, with the comfort of knowing Amgen's bid, returned that $40 per share would "not warrant further discussion." The company on July 29 increased its offer to $44 and reiterated its threat to go public with its bid, yet despite additional outreach from ChemoCentryx and Goldman Sachs officials, "Party E" would never execute a nondisclosure agreement, much less reach out to ChemoCentryx shareholders.

Based on publicly available information, Schall and Goldman Sachs representatives would tell the board Aug. 2 that "Party E" didn't have the ability to go beyond the $44 offer.

Meanwhile, one of the three companies contacted in 2020 — called "Party A" — said it likely would be interested in ChemoCentryx. What's more, Amgen on July 26 bumped up its offer to $52 per share.

And still Goldman Sachs reached out to another company, "Party G" that had been one of those contacted in May 2020, that in late July expressed interested but never followed up with the investment bankers.

Still, Schall pushed on in an Aug. 2 phone call with Bradway, saying a $54.50-per-share price would "generate interest" in board approval. By early afternoon that day, Bradway said no and Schall told the ChemoCentryx board that "Party A" was unable to consummate a transaction.

The board finally said in a meeting in the late afternoon of Aug. 2 that re-engaging the other potential acquirers or reaching out to additional companies "was not likely to lead to lead to an acquisition proposal superior (to that of Amgen), could jeopardize" the Amgen deal and cause "significant disruption and risk" to ChemoCentryx.

Through that night and into the early afternoon of Aug. ,3, ChemoCentryx and Amgen officials finalized a merger agreement, including a termination fee equaling more than $119 million.

The next day, before Wall Street markets opened Aug. 4, the companies announced the deal.

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Some addl info on the upcoming CRDF presentations -


>>> Cardiff Oncology Announces Upcoming Poster Presentations at the ESMO Congress 2022


Yahoo Finance

September 6, 2022


https://finance.yahoo.com/news/cardiff-oncology-announces-upcoming-poster-120000288.html


SAN DIEGO, Sept. 6, 2022 /PRNewswire/ -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced the publication of two abstracts that have been accepted for poster presentations at the European Society for Medical Oncology (ESMO) Congress 2022, which is taking place both virtually and at the Paris Expo Porte de Versailles in Paris, France from September 9 – 13, 2022.

Cardiff Oncology is a clinical-stage biotechnology company and our mission is to develop new treatment options for cancer patients in indications with the greatest medical need. Our goal is to overcome resistance, improve response to treatment and increase overall survival. Our investigational drug, onvansertib, a first-in-class, third-generation Polo-like Kinase 1 (PLK1) inhibitor, is being evaluated in combination with standard-of-care chemotherapy and targeted therapeutics. We are assessing tumor genomics and using our expertise in biomarker technology to rapidly evaluate patient response to treatment. (PRNewsfoto/Cardiff Oncology, Inc.)

The full texts of the published abstracts can be found on the ESMO Congress 2022 website. Details on the corresponding posters are shown below.

Poster Title:

The PLK1 Inhibitor Onvansertib Overcomes Irinotecan Resistance in RAS-mutated (mRAS) Metastatic Colorectal Cancer (mCRC) In Vivo and in Patients

Speaker:

Poster Number:

Scott Kopetz, M.D., Ph.D.

366P

Session Title:

Poster Session 7

Session Date:

September 11, 2022

Session Hours:

9:00 AM – 5:00 PM CEST

Location:

Poster Area, Hall 4

The abstract includes findings from an Expanded Access Program (EAP) in which patients with KRAS-mutated metastatic colorectal cancer (mCRC) who failed or progressed on standard-of-care, including irinotecan, were treated with onvansertib in combination with FOLFIRI/bevacizumab. These findings showed that early changes in KRAS mutant allelic frequency (MAF) were associated with increased benefit in the EAP. In addition, the abstract includes results from murine studies in patient-derived xenograft (PDX) models of RAS-mutated, irinotecan-resistant colorectal cancer. These data, together with findings from the EAP, suggest onvansertib can overcome irinotecan resistance in RAS-mutated colorectal cancer. Additional findings from the EAP and data from murine studies will be announced during the upcoming congress, in accordance with ESMO's embargo policies.

Poster Title:

Early Decreases in KRAS Mutant Allele Frequency (MAF) Predicts Clinical Benefit to the PLK1 Inhibitor Onvansertib in Combination with FOLFIRI/bev in 2L treatment of metastatic colorectal carcinoma (mCRC)

Speaker:

Poster Number:

Heinz-Josef Lenz, M.D.

397P

Session Title:

Poster Session 8

Session Date:

September 11, 2022

Session Hours:

9:00 AM – 5:00 PM CEST

Location:

Poster Area, Hall 4

The abstract includes data from an ongoing Phase 1b/2 trial evaluating onvansertib in combination with FOLFIRI/bevacizumab in second-line KRAS-mutated mCRC. The data show that the subset of patients with ≥90% decreases in KRAS MAF in circulating tumor DNA after one cycle of treatment had a significantly greater objective response rate and significantly longer progression-free survival compared to the subset of patients with decreases in KRAS MAF <90%. Additional findings from the trial will be announced during the upcoming congress, in accordance with ESMO's embargo policies.

Clinical and Corporate Update Conference Call and Webcast

Cardiff Oncology will host a webcast and conference call to provide a clinical and corporate update on Monday, September 12, 2022 at 4:30 PM ET. The event will feature discussions on the planned development pathway for onvansertib in KRAS-mutated metastatic colorectal cancer and updates on other development programs. In addition, company management will provide data updates from ongoing clinical trials. To access the call, please dial 1-877-407-9208 (domestic) or 1-201-493-6784 (international) and refer to conference ID 13731618. The conference call will also be webcast live and a link to the webcast can be accessed here. A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.

About Cardiff Oncology, Inc.

Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers. Our lead asset is onvansertib, a PLK1 inhibitor we are evaluating in combination with standard-of-care (SOC) therapeutics in clinical programs targeting indications such as KRAS-mutated metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma, and metastatic castrate-resistant prostate cancer. These programs and our broader development strategy are designed to target tumor vulnerabilities in order to overcome treatment resistance and deliver superior clinical benefit compared to the SOC. For more information, please visit https://www.cardiffoncology.com.

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The ESMO abstracts for CRDF are out and those who have seen them say the data looks good. The CC on September 12th should tell us much more.


Cardiff Oncology to Host Webcast and Conference Call to Provide a Clinical and Corporate Update on September 12, 2022
August 29, 2022
In this article:

CRDF
-1.06%

Event to feature discussions on the planned development pathway for onvansertib in KRAS-mutated metastatic colorectal cancer and updates on other development programs

Event to take place at 4:30 PM ET on Monday, September 12, 2022

SAN DIEGO, Aug. 29, 2022 /PRNewswire/ -- Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, today announced that it will host a webcast and conference call to provide a clinical and corporate update on Monday, September 12, 2022. The event will feature discussions on the planned development pathway for onvansertib in KRAS-mutated metastatic colorectal cancer and updates on other development programs. In addition, company management will provide data updates from ongoing clinical trials.

Cardiff Oncology is a clinical-stage biotechnology company and our mission is to develop new treatment options for cancer patients in indications with the greatest medical need. Our goal is to overcome resistance, improve response to treatment and increase overall survival. Our investigational drug, onvansertib, a first-in-class, third-generation Polo-like Kinase 1 (PLK1) inhibitor, is being evaluated in combination with standard-of-care chemotherapy and targeted therapeutics. We are assessing tumor genomics and using our expertise in biomarker technology to rapidly evaluate patient response to treatment. (PRNewsfoto/Cardiff Oncology, Inc.)
Cardiff Oncology is a clinical-stage biotechnology company and our mission is to develop new treatment options for cancer patients in indications with the greatest medical need. Our goal is to overcome resistance, improve response to treatment and increase overall survival. Our investigational drug, onvansertib, a first-in-class, third-generation Polo-like Kinase 1 (PLK1) inhibitor, is being evaluated in combination with standard-of-care chemotherapy and targeted therapeutics. We are assessing tumor genomics and using our expertise in biomarker technology to rapidly evaluate patient response to treatment. (PRNewsfoto/Cardiff Oncology, Inc.)
More
Details on the conference call and webcast can be found below.

Date:

September 12, 2022

Time:

4:30 PM ET

Webcast Link:

Here

U.S. Dial-in:

1-877-407-9208

International Dial-in:

1-201-493-6784

Conference ID:

13731618





A replay of the webcast will be available by visiting the "Events" section of the Cardiff Oncology website after its conclusion.

Cardiff Oncology management will also participate in two upcoming investor conferences in New York.

The Baird Global Healthcare Conference on September 13th

The H.C. Wainwright 24th Annual Global Investment Conference on September 14th.

Conference details will be made available in the coming weeks.

About Cardiff Oncology, Inc.

Cardiff Oncology is a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers. Our lead asset is onvansertib, a PLK1 inhibitor we are evaluating in combination with standard-of-care (SOC) therapeutics in clinical programs targeting indications such as KRAS-mutated metastatic colorectal cancer, metastatic pancreatic ductal adenocarcinoma, and metastatic castrate-resistant prostate cancer. These programs and our broader development strategy are designed to target tumor vulnerabilities in order to overcome treatment resistance and deliver superior clinical benefit compared to the SOC. For more information, please visit https://www.cardiffoncology.com.

Cardiff Oncology Contact:
James Levine
Chief Financial Officer
858-952-7670
[e-mail]

Investor Contact:
Joyce Allaire
LifeSci Advisors
212-915-2569
[e-mail]

Media Contact:
Amy Jobe, Ph.D.
LifeSci Communications
315-879-8192
[e-mail]

Bladerunner

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Axsome - >>> FDA approves first fast-acting oral drug for clinical depression


The Hill

by Gianna Melillo

August 22, 2022


https://www.yahoo.com/news/fda-approves-first-fast-acting-173748042.html


A newly approved treatment for clinical depression is being hailed as a potential game changer for the millions of Americans who suffer from the condition.

Auvelity, from Axsome Therapeutics, marks the first drug with a different mechanism of action approved for treating depression in 60 years.

In clinical trials, participants reported progress beginning at week one and sustained benefits throughout the study window.

A newly approved drug from Axsome Therapeutics, Auvelity, can improve symptoms of major depressive disorder (MDD) — also known as clinical depression — after one week of administration, making it the first and only oral rapid-acting drug approved for the disorder.

The drug’s mechanism is also novel and marks the first new type of medication to be approved for the condition in 60 years. Auvelity was granted Breakthrough Therapy Designation following a priority review by the Food and Drug Administration (FDA).

The announcement comes on the heels of a new review that found serotonin levels or activity are likely not the cause of depression, challenging a long-held belief the condition is the result of brain chemical imbalances and opening a window for new research on different potential treatments.

Common medicines on the market for those with MDD include selective serotonin reuptake inhibitors (SSRIs), such as Zoloft, and serotonin-norepinephrine reuptake inhibitors (SNRIs), like Cymbalta, for example, among others.

Trial results showed the positive benefits of Auvelity, an N-methyl D-aspartate (NMDA) receptor antagonist, were sustained at all time points assessed, although its exact mechanism of action in MDD remains unclear. It will become available to patients in the fourth quarter of 2022.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” said Maurizio Fava of Massachusetts General Hospital in a press release. Fava is also a Slater Family professor of psychiatry at Harvard Medical School.

The treatment comes at an opportune time as many Americans continue to suffer poor mental health outcomes resulting from the COVID-19 pandemic.

Prior to COVID-19, “over 20 million American adults experienced major depressive disorder each year,” said Michael Pollock, Chief Executive Officer of the Depression and Bipolar Support Alliance, in the release.

But research from Brown University, published in October 2021, found depression rates tripled during the first year of COVID-19 alone, while recent economic woes, global conflict and a contentious political landscape, coupled with a shortage of mental health care providers, can all compound poor outcomes.

“Nearly two thirds of patients treated with currently available antidepressants do not adequately respond, and those that do may not achieve clinically meaningful responses for up to six to eight weeks,” Fava said. “Given the debilitating nature of depression, the efficacy of Auvelity observed at one week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition.”

The FDA approval is based on a clinical trial program that tested the medication in more than 1,100 adults with depression. In addition to being superior to placebo, an additional study found the treatment superior to 150mg sustained release tablets of bupropion, a norepinephrine and dopamine reuptake inhibitor (NDRI).

Common adverse effects associated with Auvelity included dizziness, headache, diarrhea and dry mouth, among others.

“With symptom improvement happening at week one and then remission happening by week two, the combination of those two is incredibly differentiating in the marketplace right now,” said Lori Englebert, executive vice president of Axsome’s commercial and business development, in a statement. “We’re pretty excited about the product.”

The company hopes to set the price for the treatment in the coming weeks.

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>>> Why Veru Stock Is Flying High Today


Motley Fool

By Keith Speights

Aug 11, 2022


https://www.fool.com/investing/2022/08/11/why-veru-stock-is-flying-high-today/?source=eptyholnk0000202&utm_source=yahoo-host&utm_medium=feed&utm_campaign=article


KEY POINTS

Veru provided its fiscal 2022 Q3 update on Thursday.
The company announced lower revenue compared to the prior-year period and a worse net loss.

However, management is optimistic that sabizabulin will soon win authorizations for treating hospitalized COVID-19 patients.

Investors eagerly wait authorization of Veru's COVID-19 therapy.

What happened

Shares of Veru (VERU) were flying 31.6% higher at 12:14 p.m. ET on Thursday. The big gain came after the drugmaker provided its fiscal 2022 third-quarter update before the market opened.

Veru's Q3 results didn't appear to justify the sizable jump for the stock. The company reported total net revenue fell 46% year over year to $9.6 million. Its net loss totaled $22.2 million, or $0.28 per share. This result was much worse than the loss of $2.7 million, or $0.03 per share, in the prior-year period.

However, Veru's management sounded optimistic about the prospects of winning Emergency Use Authorization (EUA) for sabizabulin in treating hospitalized COVID-19 patients at high risk for acute respiratory distress syndrome (ARDS). They also expect a revenue boost from the launch of Entadfi, which treats benign prostatic hyperplasia (enlarged prostate) with a low potential for adverse sexual side effects. This positive outlook appeared to be all investors needed to pile into the biotech stock.

So what

Veru filed for U.S. EUA for the experimental drug in June. The European Medicines Agency (EMA) is reviewing potential emergency use of sabizabulin in the European Union (EU) under a new emergency regulatory pathway. The United Kingdom is also expediting a review of the drug.

It's fair to say that sabizabulin could be a game changer for Veru if it's authorized. The White House has warned of a potential major coronavirus wave in the fall and winter. Sabizabulin holds the potential to prevent thousands of deaths.

Now what

U.S., EU, and U.K. authorization decisions for sabizabulin shouldn't take very long. Veru has cranked up its manufacturing capacity and expects to be able to produce enough doses to treat around 250,000 patients per month worldwide beginning in September.

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>>> Axsome's depression drug enters competitive market after U.S. approval


Reuters

August 19, 2022

By Amruta Khandekar


https://finance.yahoo.com/news/axsome-surges-oral-depression-drug-120314009.html


(Reuters) -Axsome Therapeutics Inc on Friday gained U.S. approval for its treatment for depression, giving more than 20 million Americans affected by the disorder a new option in a market crowded by older drugs.

Shares of the U.S.-based company, which expects to launch the drug in the fourth quarter, surged 25% in early trade.

The drug, Auvelity, is a new class of treatment that reduces the symptoms of depression as early as one week, giving it a potential edge over older antidepressants, which can take up to six weeks to show effect.

The treatment has "blockbuster" potential, but the company will have to make significant investment to build the market for a new branded therapy in a field full of generic therapies, Guggenheim analyst Yatin Suneja wrote in a client note.

Major depressive disorder (MDD), or clinical depression, is characterized by persistent feelings of sadness and suicidal thoughts. Axsome estimates that the prevalence of depression rose three-fold since the start of the COVID-19 pandemic.

Newer depression treatments are few and far between, with Johnson & Johnson's nasal spray Spravato being the rare new drug to be approved in 2019 after more than 30 years.

Axsome's therapy targets several neurotransmitters including glutamate and had succeeded in a late-stage trial in 2019. The long-waited approval for the therapy comes after the agency found deficiencies in the company's application last year and extended its review of the drug.

Axsome expects the ability of patients to take the pill safely at home to boost its uptake.

The company said it was finalizing a list price for the treatment and intended to start discussions with insurers in the coming weeks.

The drug comes with a boxed warning of increased risk of suicidal thoughts and behaviors in children and young adult patients.

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>>> Axsome Therapeutics announces FDA approval of Auvelity™, the first and only oral NMDA receptor antagonist for the treatment of major depressive disorder in adults


August 19, 2022


https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-fda-approval-auvelitytm-first-and


AUVELITY is the first and only rapid-acting oral treatment approved with labeling of statistically significant improvement in depressive symptoms compared to placebo starting at one week1-4

AUVELITY uses the first new oral mechanism of action approved for major depressive disorder in over 60 years1-4

AUVELITY was developed with FDA Breakthrough Therapy designation and evaluated by the FDA under Priority Review

Company to host webcast today at 8:00 AM ET


NEW YORK, Aug. 19, 2022 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has approved AUVELITYTM (dextromethorphan HBr -bupropion HCl) extended-release tablets for the treatment of major depressive disorder (MDD) in adults.1 AUVELITY is the first and only rapid-acting oral medicine approved for the treatment of MDD with labeling of statistically significant antidepressant efficacy compared to placebo starting at one week.1-4 The rapid antidepressant effects of AUVELITY were sustained at all subsequent timepoints.1 AUVELITY is the first and only oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of MDD.3 Axsome anticipates AUVELITY to be commercially available in the U.S. in the fourth quarter of 2022.

Experience the interactive Multimedia News Release here: link

Maurizio Fava, MD, Psychiatrist-In-Chief, Department of Psychiatry, Massachusetts General Hospital, Executive Director, Clinical Trials Network & Institute, Associate Dean for Clinical & Translational Research, and Slater Family Professor of Psychiatry, Harvard Medical School said, “The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile. Auvelity, which was granted Breakthrough Therapy designation by the FDA, represents the first new oral non-monoamine-based mechanism of action approved to treat major depressive disorder in over sixty years. Nearly two thirds of patients treated with currently available antidepressants do not adequately respond, and those that do may not achieve clinically meaningful responses for up to six to eight weeks. Given the debilitating nature of depression, the efficacy of Auvelity observed at one week and sustained thereafter may have a significant impact on the current treatment paradigm for this condition.”

Michael Pollock, Chief Executive Officer of the Depression and Bipolar Support Alliance (DBSA), a leading national patient advocacy organization focusing on depression and bipolar disorder said, “The mental health crisis in the United States is one of the most pressing health issues facing our country today. Over 20 million American adults experienced major depressive disorder each year prior to the COVID-19 pandemic. These numbers increased dramatically during the pandemic with approximately thirty percent of adults in the U.S. or more than 80 million Americans experiencing elevated symptoms of depression. The need for new treatment options, particularly those with new mechanisms of action, could not be clearer and more urgent for those living with, or impacted by, major depressive disorder.”

Dan V. Iosifescu, MD, Professor of Psychiatry at the New York University School of Medicine, and Director of the Clinical Research Division at the Nathan Kline Institute for Psychiatric Research said, “Major depressive disorder is disabling and potentially life-threatening, causes profound distress for patients and their families, and leads to substantial healthcare resource utilization. Auvelity’s oral NMDA receptor antagonist and sigma-1 receptor agonist activity, which targets glutamatergic neurotransmission, provides clinicians a long sought after new mechanistic approach which may benefit the millions of patients living with this serious condition. In clinical trials, Auvelity has demonstrated rapid and statistically significant improvement in depressive symptoms as early as Week 1, and increased rates of remission at Week 2 compared with placebo. This early benefit with Auvelity was maintained and increased with continued treatment, and was accompanied by a favorable safety and tolerability profile.”

AUVELITY was studied in a comprehensive clinical program which included more than 1,100 patients with depression. The efficacy of AUVELITY in the treatment of MDD was demonstrated in the GEMINI placebo-controlled study, and confirmatory evidence which included the ASCEND study comparing AUVELITY to bupropion sustained-release tablets. In the GEMENI study, AUVELITY was statistically significantly superior to placebo in improvement of depressive symptoms as measured by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6, the study’s primary endpoint. To evaluate speed of onset of action, the change in MADRS total score from baseline to Week 1 and from baseline to Week 2 were pre-specified secondary efficacy endpoints. The difference between AUVELITY and placebo in change from baseline in MADRS total score was statistically significant at Week 1 and at Week 2.1 In the ASCEND study, AUVELITY was statistically significantly superior to bupropion sustained-release tablets 105 mg twice daily on the primary outcome measure.5 The primary outcome measure of the ASCEND study was calculated by assessing the change from baseline in MADRS total scores from Week 1 to Week 6 and then taking the average of those scores.1 In the placebo-controlled clinical study, the most common (incidence ≥5% for AUVELITY and more than twice as frequently as placebo) adverse reactions were dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis.1

The FDA granted Breakthrough Therapy designation for AUVELITY for the treatment of MDD in March 2019. This designation is granted to candidate drugs that show potential for benefit above that of available therapies based on preliminary clinical data, and it provides the sponsor with added focus from and greater interactions with FDA staff during the development of the candidate drug.6 The AUVELITY New Drug Application (NDA) was evaluated by the FDA under Priority Review, which is granted by the FDA to applications for medicines that, if approved, would provide significant improvements in the effectiveness or safety of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.

AUVELITY uses the first new oral mechanism of action in more than 60 years for MDD.1-4 AUVELITY works on the NMDA receptor, an ionotropic glutamate receptor, and on the sigma-1 receptor in the brain via its dextromethorphan component. The bupropion component of AUVELITY is an aminoketone which increases blood levels of dextromethorphan by competitively inhibiting cytochrome P450 2D6 (CYP2D6), which catalyzes a major biotransformation pathway for dextromethorphan.1 The exact mechanism of action of AUVELITY in the treatment of MDD is unclear.1 The blood levels of AUVELITY are determined by the distinct pharmacokinetic interaction between its components which has been found to be non-linear at steady state1. AUVELITY is protected by a robust patent estate extending out at least to 2037-2040.

Herriot Tabuteau, MD, Chief Executive Officer of Axsome said, “The approval of Auvelity is the culmination of the tremendous and focused research and development activities conducted by the Axsome team and our collaborators. We are extremely proud to deliver this Breakthrough Therapy-designated new treatment to the millions of patients living with depression at a time when it is most needed, given the recent sharp increase in depression prevalence. We are thrilled to contribute to potentially fundamental advances in neuropsychiatry by providing clinicians the first rapid-acting oral antidepressant demonstrated with FDA labeling, and the first oral glutamatergic medicine approved for depression. Auvelity and the rest of the Axsome neuroscience portfolio reflect our steadfast commitment to developing and delivering potentially life-changing medicines to people living with serious central nervous system disorders.”

For patients who need help getting started on AUVELITY, the Auvelity On My Side patient support program will offer comprehensive patient support services, including the Auvelity On My Side Savings Card to help make treatment more affordable for eligible commercially-insured patients. Additionally, Auvelity On My Side will include a samples program, prior authorization support, as well as other patient support tools. All programs will be available immediately upon launch.

Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric and young adult patients. Auvelity is not approved for use in children.

A Media Snippet accompanying this announcement is available by clicking on the image or link below:

Axsome Therapeutics, Inc. (AUVELITY): Media Snippet (AUVELITY)

Webcast Information

Axsome will host a webcast and conference call today at 8:00 AM Eastern to discuss the approval of AUVELITY. To access the live webcast please click here. The live webcast can also be accessed on the “Webcasts & Presentations” page of the “Investors” section of the Company’s website at axsome.com. A replay of the webcast will be available for approximately 30 days following the live event. To participate in the live conference call, please dial [phone] or for international toll-free access numbers, please click here.

About Major Depressive Disorder (MDD)

Major depressive disorder (MDD) is a debilitating, chronic, biologically-based disorder characterized by low mood, inability to feel pleasure, feelings of guilt and worthlessness, low energy, and other emotional and physical symptoms, and which impairs social, occupational, educational, or other important functioning. In severe cases, MDD can result in suicide. According to the U.S. Department of Health and Human Services, an estimated 21 million U.S. adults experienced MDD each year.7 According to the World Health Organization (WHO), depression is the leading cause of disability worldwide, and is a major contributor to the overall global burden of disease.8 Nearly two-thirds of diagnosed and treated patients do not experience adequate treatment response with available first-line treatment,9 highlighting the need for new therapies.

About AUVELITY

AUVELITY is a novel, oral, NMDA receptor antagonist with multimodal activity approved for the treatment of MDD in adults. AUVELITY is a proprietary extended-release oral tablet containing dextromethorphan HBr (45 mg) and bupropion HCl (105 mg). The dextromethorphan component of AUVELITY is an antagonist of the NMDA receptor (an ionotropic glutamate receptor) and a sigma-1 receptor agonist. These actions are thought to modulate glutamatergic neurotransmission. The bupropion component of AUVELITY is an aminoketone and CYP2D6 inhibitor which serves to increase the increase and prolong the blood levels of dextromethorphan. The exact mechanism of action of Auvelity in the treatment of depression is unclear. AUVELITY received Breakthrough Therapy designation from the FDA for the treatment of MDD.

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NIH - >>> Antiviral Nasal Spray Shows Promise Fighting COVID-19


National Institutes of Health


https://covid19.nih.gov/news-and-stories/antiviral-nasal-spray-shows-promise-fighting-covid-19


Nasal sprays may be a promising first line of defense against SARS-CoV-2 infection.

What you need to know

Prevention is the best medicine, and COVID-19 vaccines block most SARS-CoV-2 infections. But vaccines are fighting a changing opponent. New methods of fast-acting COVID-19 prevention are being researched to make it safer to be in large public gatherings like sporting events or concerts.

Researchers supported in part by the National Institute of Allergy and Infectious Diseases (NIAID) have developed a nasal spray that has the potential to not only treat COVID-19 but also prevent SARS-CoV-2 infection in a way that the virus can’t mutate to avoid. The experimental drug works in mice, and researchers believe it may be effective in humans.

What did the researchers do?

Researchers have looked for ways to prevent SARS-CoV-2 infection that the virus can’t learn to dodge or evade by mutating. To infect a cell, the virus tricks several of that cell’s proteins, including one called TMPRSS2, to gain entry. Researchers began to work on compounds that stifle TMPRSS2’s ability to interact with the viral protein.

The researchers picked four compounds that worked at very low concentrations and did not negatively affect the host cells. Those compounds were tested in human lung and colon cells that were then exposed to SARS-CoV-2. The most promising compound, N-0385, virtually stopped infection in its tracks. Because N-0385 was suitable for use as a nasal spray, researchers used a mouse model that develops severe COVID-19 and gave the mice either N-0385 or control doses of saline in their noses.

The researchers first tried one dose a day for seven days, starting a day before SARS-CoV-2 infection. When treated with N-0385, 70% of the mice survived and had little to no lung damage. When the treatment course was shortened to four days, starting one day before infection, all 10 of the mice treated with N-0385 survived. Only one of the 20 mice given saline survived.

Mice treated with just a single dose of N-0385 on the day they were infected had a high survival rate as well.

Why is this research important?

COVID-19 vaccines teach the immune system to recognize a particular protein on SARS-CoV-2 that is known as the spike protein. But the spike protein may mutate to evade immune response.

TMPRSS2 is a protein in mouse and human cells that SARS-CoV-2 uses as a gateway to infect humans. By blocking that access, compounds that target TMPRSS2 have the potential to be effective against both current and future variants.

Because we get infected with SARS-CoV-2 primarily by breathing it in, a nasal spray might be an easy and efficient way to offer protection against the virus, especially in crowded places. Researchers plan to continue testing the timing of when N-0385 should be administered and to expand testing into human clinical trials.

Where can I go to learn more?

Nasal antiviral blocks SARS-CoV-2 infection in mice

More information about the results of the study, which was funded in part by NIAID.

Finding Effective Treatments for SARS-CoV-2 Variants

The Coronavirus Immunotherapy Consortium identified new candidate drugs based on monoclonal antibodies in work funded by NIAID.

Understanding the Range of Reactions to SARS-CoV-2

In a study funded by NIAID, researchers are using mice to look for genes that account for different COVID-19 symptoms.

Sources

Lee, K. (2022, April 27). Cornell research team to develop COVID-19 nose spray treatment. Cornell Daily Sun. https://cornellsun.com/2022/04/27/cornell-research-team-to-develop-covid-19-nose-spray-treatment/

Shapira, T., Monreal, I. A., Dion, S. P., Buchholz, D. W., Imbiakha, B., Olmstead, A. D., Jager, M., Désilets, A., Gao, G., Martins, M., Vandal, T., Thompson, C. A. H., Chin, A., Rees, W. D., Steiner, T., Nabi, I. R., Marsault, E., Sahler, J., Diel, D. G., . . . Jean, F. (2022). A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic. Nature, 10.1038/s41586-022-04661-w. Advance online publication. https://doi.org/10.1038/s41586-022-04661-w

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Sparta Biomedical - >>> Stiff, achy knees? Lab-made cartilage gel outperforms the real thing


Duke Today

Aug 11, 2022


https://today.duke.edu/2022/08/lab-made-cartilage-gel-outperforms-real-thing


Human clinical trials may begin as soon as next year.

Duke researchers have developed a gel-based cartilage substitute to relieve achy knees that’s even stronger and more durable than the real thing. Clinical trials to start next year.


DURHAM, N.C. -- Over-the-counter pain relievers, physical therapy, steroid injections -- some people have tried it all and are still dealing with knee pain.

Often knee pain comes from the progressive wear and tear of cartilage known as osteoarthritis, which affects nearly one in six adults -- 867 million people -- worldwide. For those who want to avoid replacing the entire knee joint, there may soon be another option that could help patients get back on their feet fast, pain-free, and stay that way.

Writing in the journal Advanced Functional Materials, a Duke University-led team says they have created the first gel-based cartilage substitute that is even stronger and more durable than the real thing.

Mechanical testing reveals that the Duke team’s hydrogel -- a material made of water-absorbing polymers -- can be pressed and pulled with more force than natural cartilage, and is three times more resistant to wear and tear.

Implants made of the material are currently being developed by Sparta Biomedical and tested in sheep. Researchers are gearing up to begin clinical trials in humans next year.

“If everything goes according to plan, the clinical trial should start as soon as April 2023,” said Duke chemistry professor Benjamin Wiley, who led the research along with Duke mechanical engineering and materials science professor Ken Gall.

A hydrogel-based implant could replace worn-out cartilage and alleviate knee pain without replacing the entire joint.

To make this material, the Duke team took thin sheets of cellulose fibers and infused them with a polymer called polyvinyl alcohol -- a viscous goo consisting of stringy chains of repeating molecules -- to form a gel.

The cellulose fibers act like the collagen fibers in natural cartilage, Wiley said -- they give the gel strength when stretched. The polyvinyl alcohol helps it return to its original shape. The result is a Jello-like material, 60% water, which is supple yet surprisingly strong.

Natural cartilage can withstand a whopping 5,800 to 8,500 pounds per inch of tugging and squishing, respectively, before reaching its breaking point. Their lab-made version is the first hydrogel that can handle even more. It is 26% stronger than natural cartilage in tension, something like suspending seven grand pianos from a key ring, and 66% stronger in compression -- which would be like parking a car on a postage stamp.

“It’s really off the charts in terms of hydrogel strength,” Wiley said.

The team has already made hydrogels with remarkable properties. In 2020, they reported that they had created the first hydrogel strong enough for knees, which feel the force of two to three times body weight with each step.

Putting the gel to practical use as a cartilage replacement, however, presented additional design challenges. One was achieving the upper limits of cartilage’s strength. Activities like hopping, lunging, or climbing stairs put some 10 Megapascals of pressure on the cartilage in the knee, or about 1,400 pounds per square inch. But the tissue can take up to four times that before it breaks.

“We knew there was room for improvement,” Wiley said.

In the past, researchers attempting to create stronger hydrogels used a freeze-thaw process to produce crystals within the gel, which drive out water and help hold the polymer chains together. In the new study, instead of freezing and thawing the hydrogel, the researchers used a heat treatment called annealing to coax even more crystals to form within the polymer network.

By increasing the crystal content, the researchers were able to produce a gel that can withstand five times as much stress from pulling and nearly twice as much squeezing relative to freeze-thaw methods.

The improved strength of the annealed gel also helped solve a second design challenge: securing it to the joint and getting it to stay put.

Cartilage forms a thin layer that covers the ends of bones so they don’t grind against one another. Previous studies haven’t been able to attach hydrogels directly to bone or cartilage with sufficient strength to keep them from breaking loose or sliding off. So the Duke team came up with a different approach.

Their method of attachment involves cementing and clamping the hydrogel to a titanium base. This is then pressed and anchored into a hole where the damaged cartilage used to be. Tests show the design stays fastened 68% more firmly than natural cartilage on bone.

“Another concern for knee implants is wear over time, both of the implant itself and the opposing cartilage,” Wiley said.

Other researchers have tried replacing damaged cartilage with knee implants made of metal or polyethylene, but because these materials are stiffer than cartilage they can chafe against other parts of the knee.

In wear tests, the researchers took artificial cartilage and natural cartilage and spun them against each other a million times, with a pressure similar to what the knee experiences during walking. Using a high-resolution X-ray scanning technique called micro-computed tomography (micro-CT), the scientists found that the surface of their lab-made version held up three times better than the real thing. Yet because the hydrogel mimics the smooth, slippery, cushiony nature of real cartilage, it protects other joint surfaces from friction as they slide against the implant.

Natural cartilage is remarkably durable stuff. But once damaged, it has limited ability to heal because it doesn’t have any blood vessels, Wiley said.

In the United States, osteoarthritis is twice as common today than it was a century ago. Surgery is an option when conservative treatments fail. Over the decades surgeons have developed a number of minimally invasive approaches, such as removing loose cartilage, or making holes to stimulate new growth, or transplanting healthy cartilage from a donor. But all of these methods require months of rehab, and some percentage of them fail over time.

Generally considered a last resort, total knee replacement is a proven way to relieve pain. But artificial joints don’t last forever, either. Particularly for younger patients who want to avoid major surgery for a device that will only need to be replaced again down the line, Wiley said, “there just aren't very good options out there.”

“I think this will be a dramatic change in treatment for people at this stage,” Wiley said.

This work was supported in part by Sparta Biomedical and by the Shared Materials Instrumentation Facility at Duke University. Wiley and Gall are shareholders in Sparta Biomedical.

CITATION: "A Synthetic Hydrogel Composite With a Strength and Wear Resistance Greater Than Cartilage," Jiacheng Zhao, Huayu Tong, Alina Kirillova, William Koshut, Andrew Malek, Natasha Brigham, Matthew Becker, Ken Gall, and Benjamin Wiley. Advanced Functional Materials, Aug. 4, 2022. DOI: 10.1002/adfm.202205662

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>>> Sparta Biomedical Receives FDA Breakthrough Device Designation for SBM-01 Biomimetic Implant


Sparta Biopharma, Inc.

Mar 17, 2021


https://www.prnewswire.com/news-releases/sparta-biomedical-receives-fda-breakthrough-device-designation-for-sbm-01-biomimetic-implant-301249628.html


DURHAM, N.C., March 17, 2021 /PRNewswire/ -- Sparta Biomedical Inc., a developer of orthopedic solutions, today announced that its SBM-01 Biomimetic Implant has been granted a Breakthrough Device Designation from the U.S. Food and Drug Administration (FDA). SBM-01 is intended to replace damaged knee cartilage in patients having single or multiple chondral or osteochondral defects in the knee.

The Breakthrough Device Program is designed to accelerate patient access to promising technologies that have the potential to provide more effective treatments for debilitating conditions. The Program provides patients and health care providers timely access to these medical devices by assisting sponsors in their development, assessment, and review, consistent with the FDA's mission to protect and promote public health.

"The Breakthrough Device Designation reflects our team's drive to develop a truly unique solution to address a large clinical need," said Dushyanth Surakanti Co-Founder & CEO of Sparta Biomedical. "This new treatment option is designed for the hundreds of thousands of patients who experience persistent knee pain and compromised mobility after failing conservative care, but who are too young for a total knee replacement."

"This Designation will enable us to interact with the FDA more frequently to accelerate preclinical and clinical development for SBM-01," Co-Founder and COO Dimitrios Angelis added. We look forward to making this game-changing technology available to orthopedic surgeons so they may help their patients suffering from knee pain and immobility."

Osteoarthritis (OA) is one of the most common and debilitating joint disorders. The condition is characterized by progressive, irreversible articular cartilage degeneration, resulting in significant joint pain, joint motion limitations, and the formation of bony osteophytes. Most commonly, OA in the knee is first treated conservatively with non-pharmacological management, viscosupplementation injections, and anti-inflammatory medications. Patient-specific conditions, behaviors, or preferences make these options challenging to administer or achieve a high level of regimen compliance. Those who go through these interventions, often only achieve marginal temporary, palliative success.

SBM-01 Biomimetic Implant is a minimally invasive treatment for chondral or osteochondral defects of the knee cartilage. It mimics the properties of native cartilage and provides a smooth articulating surface, providing support to surrounding cartilage while stabilizing subchondral bone, and thereby limiting further exacerbation of the disease.

"SBM-01 has the potential to have a significant impact on patients who are suffering from knee cartilage damage," said Adam Yanke, MD, Ph.D., Assistant Director of the Cartilage Restoration Center for Rush University Medical Center and Assistant Professor, Department of Orthopedics. "I'm delighted that the FDA will be collaborating with us to bring this novel technology to the market as quickly as possible."

About Sparta Biomedical, Inc

Sparta's mission is to empower orthopedic surgeons with advancements that fundamentally restore movement for their patients. More information at www.sparta-biomedical.com

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Innovation Pharma - >>> Provider and Payer Analysis Supports Potential Commercialization of Innovation Pharmaceutical's Brilacidin as a Novel Oral Mucositis Drug Candidate


Accesswire

7-22-22


https://finance.yahoo.com/news/provider-payer-analysis-supports-potential-113000190.html


WAKEFIELD, MA / ACCESSWIRE / July 22, 2022 / Innovation Pharmaceuticals (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, today provided an update on the Company's Brilacidin program in Oral Mucositis (OM). Brilacidin, delivered as an oral rinse, was shown in Phase 2 clinical testing (NCT02324335) to reduce incidence, delay onset and decrease duration of severe OM (WHO Grade ≥ 3) in Head and Neck Cancer (HNC) patients receiving chemoradiation. The Company and FDA have completed an End-of-Phase 2 meeting and agreed to an acceptable Phase 3 program.

To assess current insurance programs and Brilacidin's overall commercialization potential in OM, the Company engaged separate consulting firms to analyze the provider and payer landscape -- specifically, the likelihood of clinicians to prescribe and insurers to reimburse a novel OM treatment, such as Brilacidin, should it eventually gain marketing approval. Results of this analysis are summarized below.

Large Unmet Need: Oral Mucositis (OM) presents a significant socioeconomic cost to the healthcare system and to patients, as it can substantially impact quality of life, result in hospitalization, and lead to disruptions in anti-cancer therapy and poorer outcomes. Current standard of care (SOC) treatment options (primarily devices) are lacking because they only act as symptom management and do not decrease incidence of severe OM (SOM).

Competitive Positioning: Brilacidin's oral sachet formulation was perceived as convenient and highly preferred by key opinion leaders (KOLs) in comparison to intravenous (IV) options, and KOLs are willing to prescribe Brilacidin for all HNC patients because the compound's preventative properties and ease of use as an oral rinse. Brilacidin has the potential to be a first-line product for prevention and treatment of SOM due to efficacy perceived as being highly clinically meaningful.

Development Considerations: KOLs viewed the primary endpoint of reducing SOM incidence as favorable, though recommend additional secondary endpoints to promote greater uptake (i.e., reduction of opioid usage, overall pain level, and time to onset of SOM). Maximizing overall efficacy (reduction of SOM) was identified as a higher KOL priority than the specific mechanism of action (anti-inflammatory activity) by which efficacy is achieved.

Coverage Perspectives: Developing Brilacidin as a New Drug Application (NDA), via the 505(b)(1) pathway, significantly improves Brilacidin's commercialization prospects in the OM therapeutic area. OM products, such as MuGard, GelClair, Episil, and Caphosol, which were developed as devices and not drugs, have struggled to show clinical benefit, as they are primarily palliative in nature, and from a government payer perspective are not covered under Medicare Part D.

Reimbursement Landscape: At least 2 approved drugs in all therapeutic drug classes must be made available under Medicare Part D, per USP Medicare Model Guidelines. The guidelines establish the framework (the rules) that drive payer formularies. Given there are no approved drugs for OM in HNC, should Brilacidin be approved, it is highly likely it would be included in payer formularies as a pharmacy benefit.

Commercial Opportunity: Annually, in the U.S., Brilacidin has the potential to address 52,000 OM patients in HNC, with potential future extension to 20,000 OM patients in Hematopoietic Stem Cell Transplantation (HSCT), and 160,000 OM patients in all chemotherapy categories. Based on physician estimates of Brilacidin adoption and other pricing-based assumptions, forecasts of U.S. annual sales are $188 million for OM in HNC patients in 2030, with a potential additional upside of $106 million for OM in HSCT and $598 million for OM in all chemotherapy categories.

"This analysis reinforces Brilacidin's potential to become a breakthrough OM treatment and commercialization success," said Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals. "While our focus on Brilacidin over the last few years has been in the antiviral space, given COVID-19, we have made meaningful strides to advance Brilacidin in OM, including refinement of the oral rinse formulation in sachet form. We continue to pursue partnering opportunities so Brilacidin can be further advanced in oral mucositis in the clinic."

Additional information on the Brilacidin-OM revenue opportunity based on this analysis is available on the Company's website at the link below:

https://www.ipharminc.com/new-blog/2022/7/22/brilacidin-revenue-opportunity-in-oral-mucositis

About Oral Mucositis

Oral Mucositis (OM) is a painful and debilitating complication of chemoradiation.1 Head and Neck Cancer (HNC) patients, comprising an estimated 66,000 newly diagnosed cases in the U.S. in 20212, and an estimated 900,000 worldwide3, are at high risk of developing OM. By 2030, the global incidence of HNC cases is expected to exceed 1 million per year. Moreover, between 25 and 60 percent of cancer patients, regardless of cancer type, also will experience OM. Characterized by inflammation and ulceration, patients suffering from OM are often unable to speak and eat (requiring the insertion of a feeding tube) and are more susceptible to infections, with severe cases leading to hospitalization at increased treatment costs of up to $25,000. There currently are no approved medications for the prevention of OM in the HNC population, with only limited palliative care options available. Worldwide, the OM market was estimated to be $1.5bn in 2021.4

1 The broadening scope of oral mucositis and oral ulcerative mucosal toxicities of anticancer therapies - Elad - 2022 - CA: A Cancer Journal for Clinicians - Wiley Online Library

2 Cancer Statistics, 2021 - PubMed (nih.gov)

3 Global Cancer Observatory (iarc.fr)

4 Oral Mucositis Market Size, Epidemiology, Market Research 2032 (delveinsight.com)


Alerts

Sign-up for Innovation Pharmaceuticals email alerts is available at:
http://www.ipharminc.com/email-alerts/

About Innovation Pharmaceuticals

Innovation Pharmaceuticals Inc. (IPIX) is a clinical stage biopharmaceutical company developing a portfolio of innovative therapies addressing multiple areas of unmet medical need, including inflammatory diseases, cancer, and infectious diseases. The Company is also active in evaluating other potential investment opportunities that can add value and diversify its portfolio.

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>>> Scientists reanimate dead cells in pigs, a potential breakthrough for organ transplants


NBC

by Evan Bush

August 3, 2022


https://www.yahoo.com/news/scientists-reanimate-dead-cells-pigs-150408589.html


New research is confounding conventional wisdom about life and death.

Researchers at Yale University used a new technology to restore cells in some organs of pigs that had just died, bringing the animals’ cells back to function. The findings, which were published Wednesday in the scientific journal Nature, raise profound ethical questions about how medicine defines death but also teases new possibilities for the collection of human organs for transplant.

“My eyes went wide,” Brendan Parent, an assistant professor of bioethics at the NYU Grossman School of Medicine, said about the moment he first read the new findings. “My brain went to all the crazy places we could go in 20 or 30 years.” Parent was not involved in the study, but was asked by Nature to write a commentary discussing the implications of the new technology.

The research is still in an early, experimental phase and many years from potential use in humans. It could ultimately help to extend the lives of people whose hearts have stopped beating or who have suffered a stroke. The technology also shows potential to dramatically shift how organs are collected for transplant and increase their availability to patients in need.

When the heart stops beating, blood flow is cut off from the body in a process called ischemia and a cascade of biochemical effects begins. Oxygen and nutrients are cut off from tissues. Cells begin to die. It’s a path toward death that causes damage that scientists have considered irreversible.

The new research challenges that idea.

“The demise of cells can be halted,” Dr. Nenad Sestan, a professor of neuroscience at the Yale School of Medicine and an author of the new research, said during a news conference. “We restored some functions of cells across multiple organs that should have been dead.”

The Yale researchers accomplished this feat by constructing a system of pumps, sensors and tubing that connects to pig arteries. They also developed a formula with 13 medical drugs that can be mixed with blood and then pumped into the animals’ cardiovascular systems. The research builds on previous work at Yale, which demonstrated that some damage to brain cells could be reversible after blood flow was cut off. Yale has filed a patent for the new technology, but is making its methods and protocols freely available for academic or nonprofit use, the study says.

To evaluate how well the new system, called OrganEx, works, the researchers caused heart attacks in pigs that had been anesthetized. The pigs were dead for an hour, and the researchers cooled their bodies and used neural inhibitors to ensure the animals did not regain consciousness during subsequent experiments.

Then, the researchers began to use the OrganEx system. They compared its performance against ECMO, a life-support technology used in hospitals today in which a machine oxygenates blood and circulates it throughout the body.

OrganEx restored circulation and prompted the repair of damaged cells. For example, the scientists saw heart cells contract and electrical activity return. Other organs, including kidneys, also showed improvements, the study says.

The pigs treated with OrganEx startled researchers. During experimentation, the dead pigs’ heads and necks moved under their own power. The animals remained under heavy anesthesia.

“We can say that animals were not conscious during these moments and we don’t have enough information to speculate why they moved,” Sestan said.

The researchers do view the neck jerk is an indication some muscle function was restored after death.

The OrganEx research is a single study in a laboratory setting in which researchers had total control over the circumstances of the pigs’ death and treatment. Even so, the early results open up possibilities that would have seemed like science fiction a few years ago.

“The assumption that loss of oxygen to the brain or organs within seconds to minutes means those organs are irretrievably damaged and loss — that’s not true,” said Nita Farahany, a neuroethicist and law professor at Duke University, who was not involved in the study.

The definition of death is a moving target that has shifted as new life-support technology like ventilators or ECMO were developed. Ethicists view OrganEx as ECMO on steroids and something that could change the definition of what medical death means.

“Death is a process. Technology has, at several critical moments in the course of the last several decades, shifted the goal posts for when that process begins and when we can say that the process of death has ended,” Parent, the NYU bioethicist, said. “All the iterations of machines that can sustain or restart lung function and or heart function have changed our perception, our experience, of when we can say it’s worth trying to save someone’s life.”

The Yale researchers don’t foresee the use of OrganEx to treat people anytime soon.

“Before you hook this up to a person to try to undo whole body ischemic damage in a human being, you’d need to do a lot more work. Not that it couldn’t be done, but that’s going to be a long ways away,” said Stephen Latham, director of the Yale Interdisciplinary Center for Bioethics. “There’s a great deal more experimentation that would be required.”

The implications of only partially reversing damage to a patient who suffered a deadly heart attack or who had drowned are immense, he said.

“You’d have to think about what is the state to which a human being would be restored, if they had been seriously damaged by the ischemia and you gave them kind of a perfusate that reversed some but not all of that damage. That could be a terrible thing, right?” Latham said.

Instead, the researchers see more immediate avenues for real-world use for the research. Today, transplant surgeons must scramble to stay ahead of ischemia and prevent organs from going too long without blood supply.

OrganEx could help transplant organs move longer distances and reach people who would otherwise be out of range for a transplant, Latham said. It could also prevent organs from being lost to ischemic damage, potentially expanding organ supply.

“From a transplant perspective, when every second is critical — what if it’s not? What if we have more time?” Farahany said.

The new technology’s potential opens new and compelling medical ethics questions — and adds a new twist to some that remain unresolved.

Ethicists have been debating whether it’s appropriate to use technology like ECMO to preserve organs in patients who are declared dead under cardiorespiratory criteria.

“If we decide someone is dead because their heart is stopped, but we use a technology to restart their heart — even for organ preservation — does that undermine the determination of death?” asked Parent, outlining the argument about what remains a rare practice.

There is no regulation for how long doctors must wait to determine death before restarting technology like ECMO to preserve organs for transplant, Farahany said. OrganEx could allow for more time between death and organ preservation.

It’s also possible OrganEx could change the threshold of when it’s ethical for doctors to let a patient die and then preserve their organs for donation.

“In the short run, it’s not a treatment. But if it is so effective it could be a treatment — you certainly couldn’t recover organs from somebody if you could continue to do things to save their life,” Farahany said.

It’s a technology that remains in its earliest stages, but could be impactful enough to redefine the line between life and death.

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>>> Synthetic mouse embryos with brains and beating hearts grown using only skin cells


Independent

by Maroosha Muzaffar

August 2, 2022


https://www.yahoo.com/lifestyle/synthetic-mouse-embryos-brains-beating-131824680.html


Researchers in Israel have grown a synthetic mouse embryo with a beating heart and brain – without using sperm or an egg, and outside the womb.

The embryo was grown in an artificial womb for eight days using stem cells taken from skin and cultured in a petri dish.

Stem cell scientists believe that this could be a big step in the direction of creating replacement organs for humans.

The results of the study were published on Monday in the peer-reviewed journal Cell.

Cell biologist Jacob Hanna of the Weizmann Institute of Science said this represents the first time that an advanced embryo of any species has been created from stem cells alone, according to The Times of Israel.

“It’s remarkable. There was no sperm, no egg and no uterus, but we managed to get embryos formed from stem cells alone to eight days — a third of the gestation period of a mouse — with a beating heart,” Prof Hanna said.

Previous attempts at creating an embryo without sperm and an egg had led to only the creation of blastocysts — structures formed in the early development of mammals.

Prof Hanna added that this research could one day be used to grow artificial “human embryo-like structures”.

Scientists believe that this breakthrough could help stem cell researchers understand how organs develop in embryos and then use that knowledge to develop new ways to help people with medical conditions.

Although the synthetic embryo bore a close resemblance to real mouse embryos, they were not exactly the same and did not implant or result in pregnancies in real mice, Prof Hanna added.

Alfonso Martinez Arias, a developmental biologist at Pompeu Fabra University in Barcelona, told The Washington Post that “this is an important landmark in our understanding of how embryos build themselves”.

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>>> DeepMind research predicts structure of almost every known protein


Independent

by Nina Massey

July 28, 2022


https://news.yahoo.com/deepmind-research-predicts-structure-almost-163645129.html


Artificial intelligence has mapped out the shape of virtually every protein known to science.

The breakthrough will help to tackle major global challenges such as developing malaria vaccines and fighting plastic pollution, experts say.

Proteins are the building blocks of life, and their shape is closely linked to their function.

Being able to predict a protein’s structure gives scientists a better understanding of what it does and how it works.

Our hope is that this expanded database will aid countless more scientists in their important work and open up completely new avenues of scientific discovery

The research was conducted by DeepMind and EMBL’s European Bioinformatics Institute (EMBL-EBI), which used the AlphaFold AI system to predict a protein’s 3D structure.

The AlphaFold Protein Structure Database – which is freely available to the scientific community – has been expanded from nearly one million protein structures to more than 200 million structures, covering almost every organism on Earth that has had its genome sequenced.

The expansion includes predicted shapes for the widest possible range of species, including plants, bacteria, animals, and other organisms, opening up new avenues of research across the life sciences.

Demis Hassabis, founder and CEO of DeepMind, said: “We’ve been amazed by the rate at which AlphaFold has already become an essential tool for hundreds of thousands of scientists in labs and universities across the world.

“From fighting disease to tackling plastic pollution, AlphaFold has already enabled incredible impact on some of our biggest global challenges.

“Our hope is that this expanded database will aid countless more scientists in their important work and open up completely new avenues of scientific discovery.”

In December 2020, AlphaFold was recognised as a solution to the 50-year-old grand challenge of protein structure prediction by the organisers of the Critical Assessment of protein Structure Prediction (Casp).

At the time, it demonstrated that it could accurately predict the shape of a protein, at scale and in minutes, to atomic accuracy.

The database works like an internet search for protein structures by providing instant access to predicted models.

This cuts down the time it takes for scientists to learn more about the likely shapes of the proteins they are researching, speeding up experimental work.

Earlier predictions have already helped scientists in their quest to create an effective malaria vaccine.

Scientists at the University of Oxford and the National Institute of Allergy and Infectious Diseases have been researching a protein called Pfs48/45, which is one of the most promising candidates for inclusion in a transmission-blocking malaria vaccine.

Existing technology alone did not allow them to fully understand the structure of the protein in order to see where the most effective transmission-blocking antibodies bind across its surface.

Matthew Higgins, professor of Molecular Parasitology and co-author of that study, said: “By combining AlphaFold models with our experimental information from crystallography, we could reveal the structure of Pfs48/45, understand its dynamics and show where transmission-blocking antibodies bind.

“This insight will now be used to design improved vaccines which induce the most potent transmission-blocking antibodies.”

DeepMind and EMBL-EBI said they will continue to refresh the database periodically, with the aim of improving features and functionality.

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>>> Veru Inc. (VERU), an oncology biopharmaceutical company, focuses on developing medicines for the management of cancers. Its commercial products comprise FC2 female condom/internal condom for the dual protection against unintended pregnancy and the transmission of sexually transmitted infections for ministries of health, government health agencies, U.N. agencies, nonprofit organizations, and commercial partners.

The company's development drug candidates include Enobosarm, an oral selective androgen receptor agonist that is in phase III clinical trial for the treatment of AR+ ER+ HER2- metastatic breast cancer;

Sabizabulin, which is phase IIb clinical trial for the treatment of AR+ ER+ HER2- metastatic breast cancer;

Enobosarm + abemaciclib combination therapy, which is in phase III clinical trial for the treatment of AR+ ER+ HER2- metastatic breast cancer; and Sabizabulin + enobosarm combination therapy, an oral targeted cytoskeleton disruptor plus selective androgen receptor agonist, which is in phase II clinical trial for the treatment of metastatic triple negative breast cancer.

Its drug candidates also comprise Sabizabulin, which is in Phase II clinical trial for the treatment of metastatic castration and androgen receptor targeting agent resistant prostate cancer;

VERU-100, a GnRH antagonist peptide injection, which is in Phase II clinical trial for the treatment of advanced hormone sensitive prostate cancer;

Zuclomiphene Citrate, which is in Phase II clinical trial for treating hot flashes; and Sabizabulin, which is in phase III clinical trial for the treatment of SARS-CoV-2 in subjects at high risk for acute respiratory distress syndrome.

In addition, the company is advancing a new drug formulation for the treatment of men with lower urinary tract symptoms from an enlarged prostate. The company was formerly known as The Female Health Company and changed its name to Veru Inc. in July 2017. Veru Inc. was incorporated in 1971 and is headquartered in Miami, Florida.

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>>> Xenon Pharmaceuticals Inc. (XENE), a clinical-stage biopharmaceutical company, engages in developing therapeutics to treat patients with neurological disorders in Canada. Its clinical development pipeline includes XEN496, A Kv7 potassium channel opener that is Phase III clinical trials for the treatment of KCNQ2 developmental and epilepsy encephalopathy; and XEN1101, A Kv7 potassium channel opener, which is in Phase II clinical trial for the treatment of epilepsy and other neurological disorders. The company's product candidates also comprise NBI-921352, a selective Nav1.6 sodium channel inhibitor that is in Phase II clinical trials for the treatment of SCN8A developmental and epileptic encephalopathy, and other potential indications, including adult focal epilepsy; and XEN007, A central nervous system-acting calcium channel modulator, which is in Phase II clinical trials.

It has a license and collaboration agreement with the Neurocrine Biosciences, Inc. to develop treatments for epilepsy; and with Flexion Therapeutics, Inc. to develop PCRX301 (XEN402, a Nav1.7 inhibitor) for the treatment of post-operative pain. Xenon Pharmaceuticals Inc. was incorporated in 1996 and is headquartered in Burnaby, Canada.

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>>> Xenon Pharmaceuticals Announces Closing of $287.5 Million Public Offering Including Full Exercise of the Underwriters’ Option to Purchase Additional Shares
Xenon Pharmaceuticals Inc.


GlobeNewswire

June 27, 2022


https://finance.yahoo.com/news/xenon-pharmaceuticals-announces-closing-287-181100234.html


BURNABY, British Columbia, June 27, 2022 (GLOBE NEWSWIRE) -- Xenon Pharmaceuticals Inc. (Nasdaq:XENE), a clinical stage biopharmaceutical company, today announced the closing of its previously announced underwritten public offering of 9,098,362 common shares, which includes 1,229,508 shares sold upon the full exercise of the underwriters’ option to purchase additional shares, and pre-funded warrants to purchase 327,868 common shares. The common shares were offered at a public offering price of $30.50 per common share and the pre-funded warrants were offered at a price of $30.4999 per pre-funded warrant, with each pre-funded warrant having an exercise price of $0.0001. The aggregate gross proceeds to Xenon from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Xenon, were approximately $287.5 million.

Jefferies, J.P. Morgan, SVB Securities and Stifel acted as joint book-running managers for the offering.

An automatically effective shelf registration statement relating to the securities offered in the public offering described above was filed with the Securities and Exchange Commission (SEC) on October 4, 2021. The offering was made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A final prospectus supplement and accompanying prospectus relating to the offering was filed with the SEC on June 23, 2022 and are available on the SEC’s website at www.sec.gov.

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