Replies to post #637 on Biotech Ideas

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Mind Medicine Inc (MNMD) - >>> Single dose of LSD provides immediate and lasting relief from anxiety, study says


CNN

by Sandee LaMotte, CNN

March 7, 2024


https://www.yahoo.com/lifestyle/single-dose-lsd-provides-immediate-120037213.html


A clinical trial’s encouraging results won US Food and Drug Administration breakthrough therapy status for an LSD formulation to treat generalized anxiety disorder, Mind Medicine Inc. announced Thursday. The biopharmaceutical company is developing the drug.

“A breakthrough designation is a recognition that a drug has demonstrated evidence of clinical efficacy in meeting an unmet medical need with morbidity and mortality associated with it,” said Dr. Daniel Karlin, assistant professor of psychiatry at Tufts University School of Medicine in Boston and chief medical officer for MindMed.

MindMed’s MM120 will still go through the standard FDA approval process, including phase III trials.

The designation, however, “is an offer from the agency to engage more closely in drug development,” Karlin said. “It affects timelines of response and our ability to get more interactions with the agency so that we can be sure that we’re in lockstep agreement as we move forward.”

Two other companies have also received FDA breakthrough therapy status: psilocybin for treatment-resistant depression and to MDMA, (3,4-Methyl?enedioxy?methamphetamine) commonly known as ecstasy or molly, for post-traumatic stress disorder or PTSD.

New results on efficacy at 12 weeks

A single dose of MM120 (lysergide d-tartrate) led to a 48% rate of remission from generalized anxiety disorder at 12 weeks following the drug’s administration, according to MindMed.

The MM120 drug also significantly improved clinical signs of generalized anxiety disorder for 65% of patients within three months, according to results of the phase 2b trial designed to test dosage levels, the company said.

Anxiety is the most common mental disorder in the United States, affecting over 40 million people age 18 and older each year, according to the Anxiety and Depression Association of America. Generalized anxiety order is characterized by excessive, ongoing thoughts that are difficult to control and interfere with day-to-day activities.

“The clinical improvement for many patients was more than double what we see with today’s standard of care,” Karlin said. “This occurred at all levels of anxiety, from moderate all the way up to severe.”

Standard of care for generalized anxiety disorder is a combination of cognitive behavioral therapy and medications such as selective serotonin reuptake inhibitors, or SSRIs, and buspirone — both of which work on levels of serotonin in the brain — as well as sedatives called benzodiazepines.

All of these medications need time to work and may require experimentation with various doses, adding time and expense to a patient’s treatment, Karlin said.

Determining proper dosage

The multicenter, randomized, double-blinded trial tested doses of 25, 50, 100 and 200 micrograms compared with a placebo.

“We’re very confident based on the results that 100 micrograms is the right dose to bring into our phase three studies, as we didn’t see any more improvement with 200 micrograms but did see additional adverse effects,” Karlin said.

Professor David Nutt, director of the Neuropsychopharmacology Unit at Imperial College London’s division of brain sciences, who researches psychedelics, said in an email that the study results “are very exciting data in what can be a difficult to treat population (anxiety).”

“They expand the likely utility of psychedelic treatment beyond depression,” said Nutt, who was not involved in the research. “And again, as with the depression trials, a single dose produces enduring effects, probable due to its breaking down persistent negative thought processes.”

While it was not the study’s primary purpose, results did show that MM120 also improved signs of depression, Karlin said. “We saw rapid and robust improvement on depression symptoms in people — depression and anxiety have overlapping disease definitions.”

No use of psychotherapy

Most research with MDMA and psilocybin has relied on the use of trained therapists who meet and establish a rapport with participants before the drug is administered. Those therapists are then on hand during the “trip” to help each person assimilate the experience, thus helping assure the lasting impact of any psychological insights.

The MM120 study, however, was accomplished without the use of psychotherapy during the session. Instead, monitors sat in the room to assure safety, but spent their time “mostly reading books,” Karlin said.

“While prior research has documented the benefits of combining LSD with psychotherapy to alleviate anxiety associated with life-threatening conditions, this groundbreaking study is the first to show that a single dose of LSD … can effectively treat generalized anxiety without the adjunct of psychotherapy,” said psychiatrist Dr. Gabriella Gobbi, a professor and scientist at McGill University Health Centre in Montreal and Canada Research Chair in Therapeutics for Mental Health. She was not involved in the clinical trial.

Compared with experiences with forms of LSD purchased illegally on the street, the study’s grade of MM120 did not appear to induce “bad trips,” Karlin said.

“LSD is difficult to manufacture with high purity and tends to degrade quickly in the presence of light and water,” Karlin said. “We’re manufacturing it to pharmaceutical industry standards, a highly pure version that is also shelf stable. So that’s a critical difference.”

Most adverse effects in the study were rated as mild to moderate by participants, occurring mostly on the day of the study, Karlin said. Those included euphoric feelings, illusions and hallucinations, anxiety, abnormal thinking, headaches, dizziness, nausea, excessive sweating, vomiting, numbness or tingling of the skin, and pupil dilation.

A long history of LSD research

When the MM120 clinical trial began in August 2022, it marked the first time LSD had been studied in a medical setting in over 40 years, Karlin said.

During the 1940s and early 1950s, tens of thousands of patients took LSD and other psychotropics to study their effects on cancer anxiety, alcoholism, opioid use disorder, depression, and post-traumatic stress disorder or PTSD. Researchers began to see psychedelics as possible “new tools for shortening psychotherapy.”

But when Harvard University psychologists Timothy Leary and Richard Alpert were fired from the Harvard Psilocybin Project in 1963 after the university discovered they had been giving LSD to their students, the use of psychedelics for research began to lose its luster.

Leary began to speak out publicly, encouraging young people to take LSD recreationally. He quickly became the face of the drug counterculture movement with his signature message, “Turn on, tune in, drop out.”

No longer administered solely in the relative safety of a lab or psychiatrist’s office, LSD began to feature in horror stories of bad “acid” trips at colleges and concerts — headlines that appeared alongside images of anti-Vietnam protests and Woodstock attendees.

In 1968, the United States outlawed LSD and research projects were shut down or forced underground. Then came the 1970 Controlled Substances Act, signed by President Richard Nixon. It classified all hallucinogenics, including psilocybin, as Schedule I drugs — substances with “no currently accepted medical use” and a high probability of abuse.

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[bladerunner1717]

CRDF: Change of opinion by "Seeking Alpha" analyst

Cardiff Oncology: Why The Bulls Are Winning Right Now (Rating Upgrade)

Mar. 08, 2024 7:37 PM ET Cardiff Oncology, Inc. (CRDF) Stock 8 Comments2 Likes




Galzus Research

Summary
Cardiff Oncology is focused on developing a drug for colorectal cancer and pancreatic cancer, with promising early activity shown in colorectal cancer patients.
The company is now focused on moving their drug to the first-line setting and has started a clinical trial to evaluate its efficacy.
Cardiff Oncology has a strong financial position with enough funds to operate through Q3 2025, but the success of their drug is heavily dependent on the outcomes of a single trial.


Topline Summary and UpdateCardiff Oncology (NASDAQ: CRDF) is a cancer-focused biotech working on developing a drug that exploits a novel target, particularly in colorectal cancer. In my past articles, I have been lukewarm to slightly pessimistic about their findings presented to date and their overall outlook. But recent news has sent them on a meteoric rise, and the ensuing roller coaster has readers asking me directly for input on this company. So let's examine what happened to lead to this strong rise in value, as well as where I think they might be headed next.

Pipeline UpdatesOnvansertib

Today, the PLK1 inhibitor onvansertib remains the one and only drug in development by CRDF, meaning its entire future rests on the success or failure of this agent. It is being studied mainly in a few forms of gastrointestinal cancer, namely colorectal cancer and pancreatic cancer, both representing critical unmet needs in oncology.

Most of the focus I've given in my previous writings has been for the colorectal cancer program, which has demonstrated some encouraging (though early) activity in the setting of KRAS -mutant, metastatic disease. Updated findings using add-on onvansertib with FOLFIRI-bevacizumab in the second-line setting have since been published in Clinical Cancer Research, showing a 44% response rate among 18 patients, with reasonable toxicity.

Now, the company's focus is on moving onvansertib to the first-line setting, hurdling over the typical path we have taken in targeted therapy development of starting with more "dire" clinical settings, establishing efficacy, and then moving them up. The phase 2 CRDF-004 study is seeking to randomize 90 patients with newly diagnosed, metastatic, KRAS or NRAS mutated CRC to receive first-line doublet chemotherapy plus bevacizumab, with or without one of 2 doses of onvansertib. The primary endpoint is objective response rate. CRDF announced that the first patient was dosed in this study on leap day. Initial top-line findings are anticipated later this year.

The phase 2 ONSEMBLE second-line study has been discontinued to focus on the frontline study, but CRDF provided an update in their most recent guidance that they interpret as evidence that patients who had no prior bevacizumab seemed to have better response rates, as high as 50%. It is worth keeping in mind that the patient numbers are small here, and in the standard of care, most patients with KRAS mutated mCRC are going to receive bevacizumab as part of their care, so it's difficult to interpret these findings with any real de

We've also gotten glimpses of clinical development for onvansertib in non-CRC settings. Most notably, a report of activity back in September suggests preliminary benefit from onvansertib in metastatic pancreatic cancer and extensive-stage small cell lung cancer. In particular, 4 of 21 patients with pancreatic cancer treated with add-on onvansertib (plus nal-IRI and 5-FU) yielding a 19% objective response rate, which tracks favorably with the findings from NAPOLI-1. A single response was observed with onvansertib monotherapy in the 7 patients with SCLC.

Financial OverviewAs of their most recent earnings report, CRDF held $77.4 million in total current assets, including $21.7 million in cash and equivalents, and another $53.2 million in short-term investments. Their reported annual loss was $45.4 million, with a recognized net loss of $41.4 million after interest income and other expenses.

Given these expenses, CRDF has upwards of 2 years of cash and assets on hand to fund activities, with a serious going concern emerging about a year from now at the current burn rate, by my estimation. This is consistent with guidance from the company saying they have funds to operate through Q3 2025.

Strengths and RisksStrength - CRDF's fiscal management focuses on high-priority studies

For a company in the middle of developing a drug, CRDF has a rather low cash burn rate. This could help give them time to get a data readout that propels them to the levels that we've seen recently with the likes of Janux Therapeutics, where relatively small numbers rev up a huge cash raise. Such penny-pinching stewardship is admirable, although there is a catch

Risk - Careful prioritization places most eggs in one basket

CRDF is now resting almost everything on the CRDF-004 study, and this trial is taking a risky step moving things into the frontline setting. Despite it being at the FDA's recommendation (according to the company), the observation in their 2 early studies that bevacizumab-naive patients seemed to derive the most benefit from onvansertib is shaky to me. These are small patient numbers, and I don't feel this is a hypothesis that's been carried through rigorously enough at this point.

That doesn't mean I think they're wrong, and I don't think it's a wantonly reckless step to go first line. If onvansertib really does work best in bev-naive patients, then this should end up being the exact play they need to make. But it's based on an idea that comes from pretty small patient numbers, and CRDF-004 may not generate convincing-enough findings to really show that onvansertib is moving the needle. All investors should be aware of that risk before jumping in.

Bottom-Line Summary: Why the Rating Change?As of late, developmental biotech companies are undergoing a surge of interest, with multiple companies showing promising phase 1 data sending them into market caps of billions. I do not think this is necessarily justified, but it speaks to the power of encouraging early data. CRDF, even after its recent gains, has the opportunity to surge even higher if their anticipated mid-2024 data readout in CRC shows support for their idea that onvansertib has more benefit in patients with no exposure to bevacizumab (which would be true of all first-line patients).

Tackling KRAS would be a huge coup, since there are currently no approved therapies that are specifically beneficial for patients in the frontline setting of mCRC with KRAS mutations. It's only used right now to help determine what therapies patients should not receive.

All said, I'm upgrading my rating to a "strong buy," which means that I think you should take a serious look at their portfolio and consider entering into a limited position. I would warn heavily against overextending, though, since so much of the company's value is now going to be tied to the outcomes of a single trial, and a lot can go wrong there. But it is clear now that the ceiling is too high to ignore for this company.

Bladerunner