Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Allergy warning for Pfizer/BioNTech vaccine after UK health workers with allergy history suffer reaction
https://www.cnn.com/2020/12/09/health/covid-vaccine-allergies-health-workers-uk-intl-gbr/index.html
Two people who were jabbed with Pfizer’s recently-approved coronavirus vaccine in the UK had to be treated for serious adverse reactions — leading to warnings that those with “significant” allergies may not be able to get it.
The unidentified duo — both staff in the UK’s National Health Service (NHS) — needed treatment for an “anaphylactoid reaction” Tuesday after they were among the first in the world to get the shot.
They both had serious reactions, but recovered after treatment, the NHS said.
The two staff members -- who both carried an adrenaline auto injector and had a history of allergic reactions -- developed symptoms of anaphylactoid reaction after receiving the vaccine on Tuesday. Thousands overall were vaccinated in the UK on Tuesday, NHS England told CNN on Wednesday.
The 4d radar array stuff increases range over prior radar sensors
Here’s why radar matters. In contrast to cameras and lidar, 4D imaging radar works in all conditions, offering “the highest reliability in various weather and environment conditions, including fog, heavy rain, pitch darkness, and air pollution.” It also has the benefits of sensing out to 300 meters—a requirement for higher levels of automation—and capturing doppler shifts, which show whether an object is moving toward the vehicle or away.
If Marenko’s claims are true, the 4D imaging radar can tell when a car is moving at the same speed as you, 900 feet in the distance, in the white-out conditions of a full snowstorm. It can also sense when that car slows down, or stops abruptly, and act accordingly.
He also argues that 4D imaging radar puts “a special focus” on object separation by elevation, which can help the car decide whether a stationary object up ahead is a tree branch or a person.
Thanks. In my DD I came across this blogger Michael Dekort who is critical of Musk's reliance on radar/cameras and not utilizing Lidar. Dekort is the CEO of Dactle which is a provider AV system simulation & implementation...
Dactle
https://www.dactle.com/
Dactle will provide all of the scenarios, data and integrated simulation to help you achieve a legitimate L4/5
Does TSLA use lidar or have plans to do so? Been looking at frequency-modulated continuous-wave (FMCW) lidar co's... Insight, Lumentum, Aeva & Velodyne. Lot's of SPAC activity.
Interesting back story on the development of LOXO-305...
Loxo purchased the drug from Redx Pharma for $40m in 2017 in a fire sale due to Redx being under pressure to pay off a loan that was called as a result of moving their HQ. Merck paid $2.7B for ARQL to acquire ARQ 531 and so far LOXO-305 looks superior. It appears to be quite a windfall for LLY...
Ash 2020 – UK biotech's hollow victory
https://www.evaluate.com/vantage/articles/events/conferences/ash-2020-uk-biotechs-hollow-victory
APTO's CG-806 will have a tough time beating LLY's LOXO-305...
LOXO-305 Is Highly Effective in Heavily Pretreated B-cell Malignancies
https://www.onclive.com/view/loxo-305-is-highly-effective-in-heavily-pretreated-b-cell-malignancies
More than half of patients with heavily pretreated B-cell malignancies responded to the noncovalent BTK inhibitor LOXO-305, including those with resistance or intolerance to other BTK inhibitors or BCL2 inhibitors, according to findings from the phase I/II BRUIN trial presented at the 2019 ASH Annual Meeting.
For patients with previously treated chronic lymphocytic leukemia (CLL), the objective response rate (ORR) was 77% with LOXO-305. Of these patients, 75% had received a prior BTK inhibitor. For patients with mantle cell lymphoma (MCL), the ORR was 50%, with 88% of patients having received a prior BTK inhibitor. Additionally, LOXO-305 was well tolerated, with most adverse events (AEs) being grade 1 or 2 in severity. There were no cases of atrial fibrillation or major bleeding and contusions only occurred in 11% of patients.
Taking Two Different Vaccines?
https://blogs.sciencemag.org/pipeline/archives/2020/12/02/taking-two-different-vaccines
We seem to be heading for a world with multiple coronavirus vaccines in it, and right off, I have to say that that this is a very good situation. But it has its complications, and one that I know many people have been wondering about is, what if you get two different ones?
By the spring we may well have two mRNA vaccines (Pfizer/BioNTech and Moderna), two different adenovirus vaccines (Oxford/AZ and J&J), and a recombinant protein vaccine (Novavax). We don’t have efficacy data on the J&J and Novavax candidates yet (numbers are on the way), and we can argue about the data for Oxford/AZ, but it’s certainly possible that all of them will be out there simultaneously. Putting one of these on top of the other is a step into the unknown.
MACK > saw these green flags yesterday and didn't follow through on my DD. Oh well...
http://openinsider.com/MACK
More color on AlphaFold...
In a major scientific breakthrough, A.I. predicts the exact shape of proteins
https://fortune.com/2020/11/30/deepmind-protein-folding-breakthrough/
Across more than 100 proteins, DeepMind’s A.I. software, which it called AlphaFold 2, was able to predict the structure to within about an atom’s width of accuracy in two-thirds of cases and was highly accurate in most of the remaining one-third of cases, according to John Moult, a molecular biologist at the University of Maryland who is director of the competition, called the Critical Assessment of Structure Prediction, or CASP. It was far better than any other method in the competition, he said.
Janet Thornton, an expert in protein structure and former director of the European Molecular Biology Laboratory’s European Bioinformatics Institute, said that DeepMind’s breakthrough opened up the way to mapping the entire “human proteome”—the set of all proteins found within the human body. Currently, only about a quarter of human proteins have been used as targets for medicines, she said. Now, many more proteins could be targeted, creating a huge opportunity to invent new medicines.
Thornton also said that DeepMind’s A.I. system would have profound implications for scientists who create synthetic proteins and that these could have big impacts too: everything from creating new genetically modified crop strains that will be far more nutritious to new enzymes that could help clean up the environment by digesting plastics.
Until now, the primary way to obtain a high-resolution model of a protein’s structure was through a method called X-ray crystallography. In this technique, a solution of proteins is turned into a crystal, itself a difficult and time-consuming process, and then this crystal is bombarded with X-rays, often from a large circular particle accelerator called a synchrotron. The diffraction pattern of the X-rays allows researchers to build up a picture of the internal structure of the protein. It takes about a year and costs about $120,000 to obtain the structure of a single protein through X-ray crystallography, according to an estimate from the University of Toronto.
As part of CASP’s efforts to verify the capabilities of DeepMind’s system, Lupas used the predictions from AlphaFold 2 to see if it could solve the final portion of a protein’s structure that he had been unable to complete using X-ray crystallography for more than a decade. With the predictions generated by AlphaFold 2, Lupas said he was able to determine the shape of the final protein segment in just half an hour.
Google's AI technology company DeepMind solves protein folding...
DeepMind solves 50-year-old ‘grand challenge’ with protein folding A.I.
https://www.cnbc.com/2020/11/30/deepmind-solves-protein-folding-grand-challenge-with-alphafold-ai.html
AlphaFold: a solution to a 50-year-old grand challenge in biology
https://deepmind.com/blog/article/alphafold-a-solution-to-a-50-year-old-grand-challenge-in-biology
why compelling buy now?
Right... !! is probably more like it. Absolute beast. TRIL may have the better CD47 though.
Re: OncoImmune and SACCOVID...
OncoImmune’s SACCOVID™ (CD24Fc) Exhibits Superb Therapeutic Efficacy—A Potential Breakthrough in Treating Severe and Critical COVID-19
https://www.biospace.com/article/releases/oncoimmune-s-saccovid-cd24fc-exhibits-superb-therapeutic-efficacy-a-potential-breakthrough-in-treating-severe-and-critical-covid-19/
“The interim analysis shows safety and outstanding therapeutic efficacy of SACCOVIDTM. The results indicate that patients who received SACCOVIDTM had a 60% better chance to achieve clinical recovery than those who received placebo (P=0.005). The median time to recovery was 6 days for patients treated with SACCOVIDTM compared with 10 days in the placebo group. In addition, the risk of death or respiratory failure is reduced by more than 50%,” said Dr. Pan Zheng, MD, PhD, Chief Medical Officer and co-founder of OncoImmune. Since the trial did not exclude other experimental therapeutics, many participants also received Remdesivir and/or corticosteroids including dexamethasone. Among them, those who were treated with SACCOVIDTM and Remdesivir recovered 7 days earlier than those who received Remdesivir and placebo (median time to recovery 6 days vs 13 days). Those who were treated with SACCOVIDTM and corticosteroids recovered 10 days earlier than those who received corticosteroids and placebo (median time to recovery 5 days vs 15 days). More detailed information about the trial results will be released as soon as the study is submitted to peer-reviewed medical journals.
Intel's Mobileye signs lidar agreement with Luminar, which is set to go public
https://techcrunch.com/2020/11/20/mobileye-taps-luminar-to-supply-lidar-for-its-robotaxi-fleet/
Pre-print on immunity durability in recovered COVID patients...
Immunological memory to SARS-CoV-2 assessed for greater than six months after infection
https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1
Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 185 COVID-19 cases, including 41 cases at > 6 months post-infection. Spike IgG was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.
ALXO > impressive ORR vs SOC (slide 32)...
https://ir.alxoncology.com/static-files/bee60c4d-90dc-4991-a6d5-efdb01c393f8
ALX Oncology (Nasdaq: ALXO) is a clinical-stage immuno-oncology company focused on helping patients fight cancer by developing therapies that block the CD47 checkpoint pathway and bridge the innate and adaptive immune system
ALXO > impressive ORR vs SOC (pg 32)...
https://ir.alxoncology.com/static-files/bee60c4d-90dc-4991-a6d5-efdb01c393f8
ALX Oncology (Nasdaq: ALXO) is a clinical-stage immuno-oncology company focused on helping patients fight cancer by developing therapies that block the CD47 checkpoint pathway and bridge the innate and adaptive immune system
How the ‘Dead Zone’ Could Help This Car Take on Tesla
https://www.wired.com/story/lucid-air-efficient-powertrain/
According to Carnegie Mellon University electric vehicle researchers Shashank Sripad and Venkat Viswanathan, who track the relative efficiencies of various electric powertrains and have been analyzing the Lucid Air over the past several weeks, the new car scores 218 watt-hours per mile in overall efficiency—factoring in the car’s stated range, weight, drag, frontal area, and rolling resistance—while the Tesla Model S requires 250. (The lower the number, the less energy the car consumes with each mile.) “So far most of the new EVs unveiled were not able to achieve the powertrain efficiency of Tesla,” Sripad says. “All of the previous EVs needed much bigger battery packs to achieve similar ranges because of their lower powertrain efficiencies. This car breaks the trend that all the new EVs faced when being compared to Tesla.”
Using the same metrics, the Audi E-Tron comes in at 435 watt-hours per mile in overall efficiency; the Porsche Taycan clocks in at 420; the Jaguar I-Pace and Mercedes EQC both require 365 watt-hours per mile. In a realm where hard performance and efficiency data increasingly holds as much sway in consumer minds as creature comforts and vehicle design, those can be highly persuasive numbers, helping range-nervous buyers warm up to the fancy new cars.
Novavax's vaccine as well.... NVX-CoV2373 can be stored at 2-8 degrees centigrade (36-46 F).
Derek Lowe on ramifications of cold storage requirements on distribution...
https://blogs.sciencemag.org/pipeline/archives/2020/11/09/vaccine-efficacy-data
But the other thing to keep in mind is that this candidate has (so it appears) by far the most challenging distribution of all of them. The Pfizer/BioNTech candidate, last we heard, needs -80C storage, and that is not available down at your local pharmacy. Pfizer has been rounding up as many ultracold freezers (and as much dry ice production) as they can, but there seems little doubt that this is going to be a tough one. I know that the press release talks about getting 1.3 billion doses of this vaccine during 2021, but actually getting 1.3 billion doses out there is going to take an extraordinary effort, because you’re getting into some regions where such relatively high-tech storage and handling becomes far more difficult. Population density is as big a factor as electricity and transport infrastructure. With demanding storage requirements, the more people that are within a short distance of a Big Really Cold Freezer, the better. And the more trucks (etc.) that you have to send down isolated roads to find the spread-out patients, the worse. That’s always the case, but if you’re rushing against dry-ice-pack deadlines the situation is more fraught.
CRDF > Only caveat is all data is for combo...no monotherapy.
CMS guidance on administering COVID mAbs...
https://www.cms.gov/files/document/03092020-covid-19-faqs-508.pdf
Pg 121...
Question: CMS has established flexibilities under the Hospital Without Walls initiative to allow hospitals to furnish care in temporary expansion sites, including erected tents, retrofitted convention centers and beneficiaries’ homes. Would hospitals also be able to use these same flexibilities to furnish monoclonal antibodies in temporary expansion sites?
Answer: In response to the COVID-19 Public Health Emergency (PHE), CMS issued several 1135 waivers of certain hospital conditions of participation and the provider-based rules, in order to allow hospitals to furnish hospital services, including drug administration, in temporary expansion sites. These Hospital Without Walls flexibilities could be used by hospitals to furnish monoclonal antibodies in temporary expansion sites, such as an erected tent, a retrofitted convention center, or the beneficiary’s home, consistent with the terms of the EUA or FDA approval, as applicable. Hospitals that previously constructed expansion sites at the beginning of the PHE, and were approved under earlier 1135 waivers, are able to continue using those sites so long that they continue to meet the conditions of participation that remain in effect during the COVID-19 PHE.
Further, as previously announced in the April 30, 2020 Interim Final Rule (85 FR 27559-62), hospitals that temporarily relocate an existing on-campus or excepted off-campus provider based department in order to furnish outpatient care in a temporary expansion site may
wish to submit a temporary relocation exception request to their Regional Office, which would enable them to continue to be paid under the Outpatient Prospective Payment System for services furnished at the relocated department. More information about the Hospitals Without Walls flexibilities and the temporary extraordinary circumstances relocation exception can be found here.
New: 10/28/20
REGN > antibody cocktail reduced Covid-19 related medical visits by 57%...
REGENERON'S COVID-19 OUTPATIENT TRIAL PROSPECTIVELY DEMONSTRATES THAT REGN-COV2 ANTIBODY COCKTAIL SIGNIFICANTLY REDUCED VIRUS LEVELS AND NEED FOR FURTHER MEDICAL ATTENTION
https://investor.regeneron.com/news-releases/news-release-details/regenerons-covid-19-outpatient-trial-prospectively-demonstrates/
Virologic results (n=524, prospectively confirming previous 275-patient analysis):
On the primary endpoint, the average daily change in viral load through day 7 (mean time-weighted average change from baseline) in patients with high viral load (defined as greater than107 copies/mL) was a 0.68 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p<0.0001). There was a 1.08 log greater reduction with REGN-COV2 treatment by day 5, which corresponds to REGN-COV2 patients having, on average, a greater than 10-fold reduction in viral load, compared to placebo.
In the overall patient group with detectable virus at baseline, the average daily reduction in viral load through day 7 was a 0.36 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p=0.0003).
As in the earlier analysis, patients with higher viral load at baseline and/or no detectable antibodies at baseline (suggesting their bodies had not yet mounted an effective immune response), derived greater benefit from REGN-COV2 therapy.
Clinical results in the overall population (n=799):
On the key clinical endpoint, treatment with REGN-COV2 reduced COVID-19 related medical visits by 57% through day 29 (2.8% combined dose groups; 6.5% placebo; p=0.024).
Treatment with REGN-COV2 reduced COVID-19 related medical visits by 72% in patients with one or more risk factor (including being over 50 years of age; body mass index greater than 30; cardiovascular, metabolic, lung, liver or kidney disease; or immunocompromised status) (combined dose groups; nominal p = 0.0065).
Lotemax is .5% suspension dosed 4X day...Eysuvis is .25% dosed 2X day. Lotemax vs. other steroids....
Impact of the Topical Ophthalmic Corticosteroid Loteprednol Etabonate on Intraocular Pressure
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846687/
In early pivotal clinical trials of LE ophthalmic suspension for conjunctivitis (allergic, giant papillary), anterior uveitis, and post-operative inflammation, LE had minimal impact on IOP over short-term (<28 days) and long-term (≥28 days) use.
In all studies, LE consistently demonstrated a low propensity to elevate IOP, regardless of formulation, dosage regimen, or treatment duration, including in known steroid responders. The cumulative proportion of patients exhibiting clinically significant IOP increases was 0.8% (14/1725 subjects) in studies evaluating short-term LE treatment and 1.5% (21/1386 subjects) in long-term studies. Furthermore, use of LE was associated with significantly lower rates of IOP elevation ≥10 mm Hg as compared to prednisolone acetate or dexamethasone (when used in combination with tobramycin). The cumulative data to date substantiates a favorable IOP-safety profile for LE with both short-term and long-term use.
Loteprednol etabonate (LE) is unique among corticosteroids in that the drug molecule incorporates a metabolically labile moiety which allows rapid metabolism and degradation following glucocorticoid receptor activation, thereby imparting a lower risk of side effects [21–23]. Unlike other ophthalmic corticosteroids, LE contains a chloromethyl ester instead of a ketone moiety at the carbon 20 (C-20) position of the prednisolone acetate (PA) core structure (Fig. 1). The metabolically labile C-20 ester group undergoes predictable hydrolysis by endogenous esterases into inactive metabolites (Fig. 1). In addition, LE is highly lipophilic and binds the glucocorticoid receptor with 4.3-fold greater affinity than dexamethasone [24]. LE also retains the high potency of prednisolone, with an anti-inflammatory efficacy 20-fold higher than hydrocortisone [22]. These attributes enable LE to penetrate the ocular tissues including the conjunctiva, cornea, and iris-ciliary body, bind to the glucocorticoid receptor, and exert potent anti-inflammatory effects, with minimal propensity for side effects.
Eysuvis was trialed against placebo so no data vs. Lotemax and Lotemax wasn't trialed for DED flares. The SE profile is benign...AEs (2.9% vs 1.5% placebo) and IOP elevation (0/449) similar to placebo.
Lotemax is dosed .5% and Eysuvis .25%.
My understanding is pts are frustrated with how long it takes to get relief with Restasis(cyclosporine) and Xiidra. Both have significant side effects upon initiation and can take weeks if not months before the patient gets relief and that translates to a high discontinuation rate (60-70% within 2-3 mos)). Both Restasis and Xiidra must be taken continuously which becomes expensive. According to surveys 82% of Restasis and Xiidra pts suffer from flares. The DED population is severely underserved...90% of DED pts are not on either Rx and 80-90% of DED pts suffer from flares.
For dry eye flares Eysuvis works much faster than Restasis or Xiidra...within 2 days the patient feels less discomfort. Lotemax (Bausch & Lomb) is the same drug (loteprednol etabonate) as Eysuvis except Eysuvis uses a proprietary nanoparticle delivery technology (AMPPLIFY) which increases LE penetration to corneal and aqueous humor by more than 3x. Lotemax is not approved for DED flares but some optometrists have been prescribing Lotemax off-label. Currently about 3% of the 17.2M DED pts are prescribed off-label steroids. The KALA investment thesis is that optometrists will switch from off label steroids i.e. Lotemax to Eysuvis for flares, will also prescribe Eysuvis when starting pts on Restasis or Xiidra and will switch those who discontinue to Eysuvis with the aim of prescribing 4-5 cycles over a yr. The average patient experiences 2 to 7 dry eye flares on a yearly basis.
some perspectives on flares from a few eye docs...
https://www.eyeworld.org/download/file/fid/453#:~:text=The%20average%20patient%20experiences%202,eye%20flares%20throughout%20the%20year.
Rapid relief
Richard Lindstrom, MD, noted that he understands the expectations and demands of these patients for several reasons including that he has firsthand experience with dry eye symptoms. “I have mild dry eye and I experience flares that are primarily a result of environmental influences.
When these flares occur, I want a solution that produces a rapid response. I want something that is powerful and potent and works fast,” he said. Although artificial tears may provide some palliative relief, they do not address the underlying inflammation that is the primary driver of a flare and thus are typically insufficient to provide adequate relief. Likewise, currently approved anti-inflammatory therapies may be appropriate for chronic management but not for episodic symptom flares, as the onset of relief is not rapid enough for acute symptom relief from a dry eye flare.
Dr. Donnenfeld said that addressing this need is paramount. “Dry eye flares are an extraordinarily common part of dry eye management. Although there are excellent dry eye therapies available, we haven’t had therapeutics specifically for managing dry eye flares. This opens up a new avenue for managing dry eye because patients who are on maintenance therapy but still have flares are not happy with their treatment,” he said. “The majority of dry eye patients are not on therapy and they may just have episodic dry eye that occasionally flares up, and a periodic short course of therapy might be adequate for them,” he continued. “However, most patients who are on maintenance therapy, whether it be artificial tears, immunomodulators, or oral medications, still experience flares throughout the year as well.”
Dr. Kabat: Until the late 1990s, drug therapy for dry eye was
unheard of. We had artificial tears, which accounted for as
much as 80% of our therapeutic management, and the re-
mainder of patients became candidates for punctal occlusion.
Dr. Steven Pflugfelder and other pioneers showed us that
anti-inflammatory medications could provide significant relief
for those suffering from dry eye,19 but many of us hesitated
because the approach involved off-label use of a corticoste-
roid—a drug class that we had been taught was to only be
used in extreme cases and with the utmost caution. When
topical cyclosporine was introduced in 2003, we were initially
elated to finally have a medication that was specifically indicat-
ed for treating keratoconjunctivitis sicca. However, we quickly
found that a good percentage of patients failed to respond
to this new formulation in the manner that we had hoped.
Moreover, it was very difficult to predict which patients would
succeed and which would ultimately fail or discontinue therapy
because of intolerability, cost issues, or simply frustration.
My biggest challenge in developing an effective treatment
regimen for dry eye is two-fold. First, it has taken many years
to realize that not all dry eye is alike in its composition or man-
ifestations, and, hence, there is no single therapy that works
for every patient. A good dry eye doctor understands that, to
be successful, one must first identify the most significant con-
tributory element of the ocular surface disease and manage it
aggressively through whatever means are most appropriate.
Second, when inflammation is present, we can no longer af-
ford to use agents that take up to six months to begin yielding
improvement. If my experience has taught me anything, it’s that
patients are not very patient! The symptomatic individuals who
I see today want and expect relief, or at least some indication
of recovery, in a matter of days or perhaps weeks. If I’m lucky,
they may give me one or two months.
KALA > bull & bear case...
Jefferies...
As previously reported, Jefferies analyst Biren Amin downgraded Kala Pharmaceuticals to Hold from Buy with a price target of $10, down from $21 after surveying 25 ophthalmologists and 25 optometrists who are based in the U.S. and treat an average of 224 dry eye disease patients per month. While Amin expects FDA approval for Eysuvis by its October 30 PDUFA date, the eye care professionals surveyed estimated Eysuvis could capture 12% market share at launch in year one and 13% in year two, assuming a price of $280/bottle, said Amin, who believes the company is evaluating a price in the range of $300-600/bottle. Most of the survey doctors pointed to product cost and insurance coverage as the main hurdle to strong Eysuvis adoption, added Amin.
Kala’s Eysuvis FDA approval represents an important milestone for the company, with the product approved for both the sign and symptoms of short-term dry eye disease (as expected). At the same time, expectations have built ahead of today’s FDA decision with a ‘sell the news’ event on the product approval, with KALA shares down 15% ($60mm of market cap, vs S&P Biotech up ~1%) as investor focus now shifting to a near-term product launch in 4Q20 and into 2021.
Overall, we see today’s share pullback as a meaningful buying opportunity, with two FDA approved products and Eysuvis, the company’s lead product, holding a significant dry eye market opportunity where we forecast >$750mm peak sales (which could prove conservative). We highlight a) significant unmet need in the acute dry eye market, with Eysuvis representing the first approved treatment, and b) strong B/S position with $159mm in cash to support the product launch and operations thru mid-2022. With KALA shares trading at a ~$375mm market cap and <$7/share, we see an attractive valuation and risk/reward opportunity into the Eysuvis launch with several hundred million annual sales opportunity expected by 2024. Reiterate OW.
• Eysuvis approved for both the sign and symptoms of short-term dry eye disease. Today, Kala announced the FDA approval for Eysuvis, the company’s lead product, for short-term dry eye disease, representing the first approved FDA treatment to offer rapid relief for acute dry eye symptoms. The Eysuvis approval is in line with our expectations with an FDA label for both the signs and symptoms of dry eye disease and no restrictions on continued prescription refills.
• Acute dry eye represents a significant market opportunity with no approved treatment currently. We forecast Eysuvis peak sales of >$750mm on fairly conservative assumptions for both product pricing (below chronic dry eye therapies) and market penetration (among ~17mm US diagnoses dry eye patients), with upside to >$1bn potential peak sales. Our physician feedback indicates significant unmet need for an acute dry eye treatment, with patients of nearly all severity levels experiencing intermittent flares. Further, there are currently no approved products on the market or late-stage competitors that offer rapid relief for short-term acute dry eye symptoms within a few days.
• Kala will leverage its existing sales & marketing infrastructure to launch Eysuvis. Kala’s existing Inveltys salesforce overlaps completely with the target Eysuvis ophthalmology prescribing base, and Kala plans to further expand its sales force to ~100-125 reps with the Eysuvis launch over time. Overall, we would expect faster uptake / reimbursement decisions on Eysuvis relative to the company’s Inveltys launch given the significant unmet need with no currently approved product and a majority of patients on commercial insurance.
• We see a highly attractive risk/reward for Kala into Eysuvis product launch in 4Q20 and into 2021. With the recent KALA share pullback, we see an attractive risk/reward into the Eysuvis launch with the company well capitalized to support the product’s dry eye launch with mid-2022 cash runway. On valuation, KALA trades at only at a ~$375mm market cap ($7/share), and we see shares as significantly undervalued with annual sales potential of several hundred million by 2024, assuming the company executes on launch plans over the next 12-24 months. Further, we see limited downside given the company’s extended IP life and two FDA approved products.
• Kala is well capitalized to support pending Eysuvis and ongoing Inveltys product launches. Kala ended 3Q 2020 with $159.1 of cash on the balance sheet, which the company expects will fund operations through at least 3Q 2022.
Why the KALA selloff?
KALA > Kala Pharmaceuticals Announces FDA Approval of EYSUVIS™ for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease
https://investors.kalarx.com/news-releases/news-release-details/kala-pharmaceuticals-announces-fda-approval-eysuvistm-short-term
EYSUVIS utilizes Kala’s AMPPLIFY® mucus-penetrating particle (MPP) Drug Delivery Technology to enhance penetration of loteprednol etabonate (LE) into target tissue on the ocular surface. LE targets the immune responses that drive acute dry eye disease flares. Prior to EYSUVIS, there were no FDA-approved ocular corticosteroids for the treatment of dry eye disease. Kala Pharmaceuticals plans to launch EYSUVIS in the U.S. by year-end.
Here's another study supporting aspirin for COVID...
Aspirin Use is Associated with Decreased Mechanical Ventilation, ICU Admission, and In-Hospital Mortality in Hospitalized Patients with COVID-19
https://journals.lww.com/anesthesia-analgesia/Abstract/9000/Aspirin_Use_is_Associated_with_Decreased.95423.aspx
Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days prior to admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin vs. 48.4% non-aspirin, p=0.03) and ICU admission (38.8% aspirin vs. 51.0% non-aspirin, p=0.04), but no crude association with in-hospital mortality (26.5% aspirin vs. 23.2% non-aspirin, p=0.51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR 0.56, 95% CI 0.37-0.85, p=0.007), ICU admission (adjusted HR 0.57, 95% CI 0.38-0.85, p=0.005), and in-hospital mortality (adjusted HR 0.53, 95% CI 0.31-0.90, p=0.02). There were no differences in major bleeding (p=0.69) or overt thrombosis (p=0.82) between aspirin users and non-aspirin users.
Conclusions:
Aspirin use may be associated with improved outcomes in hospitalized COVID-19 patients. However, a sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.
Brazilians Turn to Botox to Wipe Away That Quarantine Frown
Demand for beauty treatment soars for men and women alike during pandemic, as videoconferences and masks highlight wrinkles
https://www.wsj.com/articles/brazilians-turn-to-botox-to-wipe-away-that-quarantine-frown-11603645858?mod=hp_featst_pos5
SÃO PAULO—With face masks obligatory across many Brazilian cities, the wealthy are relying ever more on Botox to get the perfect, wrinkle-free forehead. Beauty clinics say demand for the cosmetic treatment has as much as doubled here since the pandemic began.
“People now look each other in the eye more, in the eyes and the forehead—just where their wrinkles are,” said Aline Medici, who owns a franchise of 21 beauty clinics across Brazil, Ad Clinic, with her husband. Over the past few months, they struck deals to open another nine clinics, even as the country plunged into recession.
While face masks have brought scrutiny to the forehead and region around the eyes, the traditional areas for Botox injections, dermatologists also attribute the boom to videoconferencing. After months of staring at themselves during Zoom calls, Brazilians—many only in their early 30s—have emerged from lockdown convinced they need cosmetic help.
“I couldn’t bear looking at my face any longer,” said Deliza Costa, a 32-year-old sales executive, who had Botox injected in June. “It seemed like I was frowning the whole time. I ended up paying more attention to my face than the call.”
Brazil was a world leader in cosmetic treatments even before the pandemic. With a fraction of the per capita income of rich nations, Brazil performed more plastic surgeries than any other country in the world in 2019, according to the International Society of Aesthetic Plastic Surgery. For nonsurgical procedures such as Botox, it ranked third, behind the U.S. and Japan.
While data on Botox injections this year in Brazil isn’t yet available, dermatologists and beauty clinics in major cities such as São Paulo and Rio de Janeiro say they are carrying out around 20% to 100% more treatments a month than they did before the pandemic. It is partly due to pent up demand, they say, after many establishments closed down in March and April. However, they are also seeing an influx of Botox first timers. Many of them are men.
“I’ve never done so much Botox as I have during the pandemic, and I’ve never seen so many men coming in,” said Eliandre Palermo, head of the São Paulo branch of Brazil’s Society of Dermatology, who has her own clinic in the city. The number of new clients increased by 60% during the pandemic, she said.
Many men were cajoled into getting Botox by their wives after spending months cooped up together during lockdowns, dermatologists said.
“I was worried my friends would make fun of me,” said Luis Ferreira, a 32-year-old pharmaceutical representative, who got a Botox treatment in July. He said he had never spent so much time with his girlfriend before the pandemic and had learned a lot about cosmetic treatments during their lockdown. He now recommends it to his male friends. “I tell them: ‘Do it, dude! It’s important to look good!’ ”
Men now account for about 20% of Ad Clinic’s Botox patients, compared with 5% before the pandemic, said Ms. Medici.
“When you take a photo, you pose to look your best,” said Ligia Kogos, a dermatologist in São Paulo who has been injecting Botox into Brazilians’ faces since the 1990s. But in videoconferencing, “you see your face there at the bottom of the screen, you see yourself speaking, working, your facial muscles contracting.”
With many beauty clinics closed during the height of the pandemic, Brazilians turned to dentists. In Brazil, dentists are authorized to administer Botox as the substance can be used to treat conditions such as jaw clenching. In reality, many use it to treat their patients’ wrinkles—the subject of a long-running judicial dispute with dermatologists who say the dentists are unqualified.
“I closed for three months and my patients would hassle me every day, asking me to find a way to inject them or go to their house,” said Márcia Rosita Garcia, who has a beauty clinic in São Paulo. “A lot of them ended up going to orthodontists.” She said many of her patients had gone through breakups during lockdown and saw Botox as a way to feel good about themselves again.
The stress of the pandemic itself has also worsened patients’ wrinkles as high amounts of the stress hormone cortisol can affect the skin’s collagen, said Kaliandra Cainelli, who has seen demand for Botox rise 20% at her two clinics in Rio de Janeiro.
Dermatologists elsewhere in cities such as Los Angeles and London have also reported rising interest in Botox, but the trend has been particularly pronounced in Brazil. Demand for beauty treatments and products has grown even as the economy shrunk by a record near-10% in the second quarter and the country became a global hot spot for the disease, registering more than 150,000 deaths from Covid-19.
Producers of eye creams, used to reduce wrinkles and dark circles, sold 30% more in the first six months of this year compared with 2019, according to data compiled for the Journal by the Brazilian Association of the Cosmetic, Toiletry and Perfumery Industry. Google searches for “skin care” surged 66% between February and April, while online sales of beauty products between January and August doubled from the same period a year earlier, according to the Brazilian Association of Electronic Commerce.
For some image-obsessed Brazilians, face masks and videoconferencing have also provided the perfect way to hide bruising and bandages from more serious treatments. Google searches for rhinoplasty, or nose jobs, have skyrocketed in Brazil since March. Plastic surgeons say other patients have made the most of working over Zoom to get liposuction and other work done from the neck down.
“I did lipo on my stomach and legs and got breast implants,” said Zoe Gardini, a 45-year-old architect, adding that the lockdown meant that she didn’t have to take time off work to recover. “I’ve wanted to get implants for a while but when else can I go three weeks without driving?”
Write to Samantha Pearson at samantha.pearson@wsj.com
PRAX > from the S-1...
https://www.sec.gov/Archives/edgar/data/1689548/000119312520269768/d945651ds1a.htm
We are developing PRAX-114, an extrasynaptic-preferring GABAA receptor positive allosteric modulator, or PAM, for the treatment of patients suffering from major depressive disorder, or MDD, and perimenopausal depression, or PMD. PRAX-114 is under development as a potentially differentiated treatment as both a monotherapy and adjunctive therapy for both the acute and maintenance setting. We have a multi-cohort, three-part Phase 2a clinical trial ongoing in Australia, and in Part A of the trial, we observed marked improvements in depression scores in MDD patients within two weeks of treatment. We expect complete topline data from Part B of the trial in the second half of 2021 and from longer-term dosing in MDD patients in Part C of the trial in the fourth quarter of 2020. We are planning to initiate a Phase 2/3 trial in the United States and Australia in the fourth quarter of 2020, which is intended to satisfy one of two registrational trials required by the U.S. Food and Drug Administration, or the FDA, to support clinical efficacy for the treatment of MDD, and we expect topline data in the second half of 2021.
There is significant unmet medical need in MDD and PMD with over 22 million individuals
We believe that our PRAX-114 program has several advantages as compared to currently available therapies and product candidates in the GABAA PAM therapeutic class:
? Wider Therapeutic Window. We have determined that PRAX-114 is an approximately 10.5-fold more potent PAM of the extrasynaptic form of GABAA receptors compared to the synaptic form. By preferentially modulating extrasynaptic GABAA receptors, we believe PRAX-114 has the potential to mediate antidepressant and anxiolytic activity without the significant sedation observed with less selective neuroactive steroids.
? Patient-Centric Dosing. We believe the ability to administer PRAX-114 with or without food is key for clinical and commercial success in MDD and is critical for a patient-centric therapeutic, as many patients with depression suffer from appetite disturbance. We have observed fast absorption of PRAX-114 within one to three hours of dosing and a robust pharmacokinetic, or PK, profile across multiple trials. Based on clinical findings to date, we believe that PRAX-114 does not need to be taken with food to achieve therapeutic exposure, whereas other GABAA PAMs may require food to achieve therapeutic exposure.
? Sustained Administration. After consultation with the FDA and other stakeholders in MDD and PMD therapy, we designed our Phase 2/3 trial of PRAX-114 to include 28-day nightly dosing to evaluate patients at both 14 days to assess the rapidity and robustness of response and 28 days to evaluate durability of effect. We believe that having a dosing paradigm consistent with the duration of depressive episodes will provide the most substantial benefit to patients in controlling their disease, further differentiating PRAX-114 from other GABAA PAMs.
? Indication Expansion. Because PRAX-114 has demonstrated a novel pharmacology and, to date, has a well-tolerated profile, we believe PRAX-114 is suitable for potential development across a wide-range of indications in psychiatry and neurology, providing sizable expansion opportunities to explore in addition to MDD.
Aubrey Rankin was CEO of Zeltiq from from Aug 2013 - Aug 2015. He started HintMD in Sept 2015...1 mo. after AGN acquired Zeltiq. Rankin is now President, Innovation & Technology at Revance. Rankin also has extensive M&A experience which is a plus...
https://www.linkedin.com/in/aubreyrankin
Because I didn't read the prospectus it wasn't old news to me. However after reading it I found the "Background of the Merger" (beginning on pg 95) a very interesting read. Any idea as to the identity of the mysterious "Party B" who was the competing bidder against Revance who made an all cash offer? According to the prospectus Party B was an investor in HintMD and a "global pharmaceutical company" undergoing "certain reorganization activities" according to the prospectus... ABBV/AGN? I'm guessing Zeltiq was a seed investor because Aubrey Rankin the co-founder of HintMD was CEO of Zeltiq...then AGN inherited shares when they acquired Zeltig and AVVB inherited those shares when they acquired AGN.
https://www.sec.gov/Archives/edgar/data/1479290/000119312520177782/d922558d424b3.htm
In early January 2020, Mr. Rankin and Mr. Kos met with a senior officer of a global pharmaceutical company (“Party B”), which is also an investor in HintMD. During the meeting, Mr. Rankin shared that a third party had expressed interest in acquiring HintMD, and the representative of Party B indicated that Party B may also be interested in acquiring HintMD. Over the course of the week, Mr. Rankin and Mr. Kos had multiple conversations with Party B’s management about the potential benefits of a combination to the respective businesses.
On April 18, 2020, HintMD delivered a revised indication of interest to Party B. The revised indication of interest provided for an up-front cash payment of $125 million to the stockholders other than Party B, which reflected an implied equity value of HintMD on a fully diluted basis (assuming the forgiveness of outstanding debt held by Party B) of approximately $140 million as well as an additional amount of contingent cash consideration (subject to the achievement of milestones) with up to $275 million to the stockholders other than Party B, which implied an additional aggregate dollar amount on a fully diluted basis of up to approximately $308 million.
The committee was also concerned that the Party B transaction presented a significant amount of execution risk in terms of getting to a signed definitive agreement, particularly in light of certain reorganization activities occurring at Party B, which had already contributed to Party B’s delay in presenting an indication of interest.
The committee also revisited the execution risk presented by the Party B transaction, including as a result of the pending departure of HintMD’s primary business contact at Party B, and the committee was particularly concerned that if the transaction with Party B failed in the coming months, that HintMD could be in a position where it had no investors for a new round of financing, no ability to reengage with Revance on a potential transaction and no funds to operate its business at the end of June 2020. The committee also considered that further delay to the Revance transaction in order to pursue the Party B transaction could result in Revance decreasing its offer or terminating discussions altogether. Following the discussion, the committee concluded that the transaction with Party B presented too great a risk to HintMD (including in terms of execution risk and purchase price risk), and that the company should move forward with the Revance transaction and enter into exclusivity.
Following the meeting of the HintMD transaction committee, HintMD executed the indication of interest and entered into the exclusivity agreement with Revance.
On February 6, 2020, Mr. Foley in his capacity as the Chief Executive Officer of Revance reached out to Mr. Rankin to share Revance’s interest in exploring a potential acquisition of HintMD. Mr. Foley also informed Mr. Rankin that he had recused himself from the Revance board and management process and that he intended to inform the Chief Operating Officer of Party B that he would be recusing himself from the HintMD process.
It was disclosed in the Prospectus filed on June 24...
https://www.sec.gov/Archives/edgar/data/1479290/000119312520177782/d922558d424b3.htm
Interests of Revance Directors and Executive Officers in the Merger (see page 109)
In considering the recommendation of the Revance board with respect to the Merger, you should be aware that certain members of the Revance board and certain executive officers of Revance have interests in the Merger that may be different from, or in addition to, the interests of Revance stockholders, which include:
Mark Foley, Revance’s Chief Executive Officer and a member of the Revance board, previously served on the HintMD board and was the Chairman of the board of directors from October 2017 until May 2020 and is a holder of 817,383 shares of HintMD common stock. Mr. Foley is also the trustee of the Foley Family Trust, which holds 121,182 shares of HintMD Series A-1 preferred stock and 36,195 shares of HintMD Series B-2 preferred stock.
Each of the HintMD board and Revance board was aware of these interests and considered them, among other matters, in approving the Merger Agreement and, in the case of the HintMD board, in making its recommendation that HintMD stockholders adopt the Merger Agreement.
RVNC > a Form 4 filed today reveals CEO Mark Foley was a shareholder of HintMD. He received 315,352 shares of RVNC for his ownership stake in HintMD. Dew - what do you make of this?
On July 23, 2020. the Issuer completed acquisition (the "Merger") of Hint, Inc. ("HintMD") pursuant to that certain Agreement and Plan of Merger, dated as of May 18, 2020, by and among the Issuer, HeartMerger Sub, Inc., direct wholly-owned subsidiary of the Issuer, HintMD, and Fortis Advisors LLC, solely in its capacity as the securityholders' representative (the "Merger Agreement"). Pursuant to the terms of the Merger Agreement, at the closing of the Merger, the shares held by Mr. Foley and the Foley Family Trust in HintMD were automatically cancelled and converted into the right to receive shares of common stock of the Issuer.
>>>However, RVNC's dollar sales in CD will naturally be lower at a dose of 125U as compared to a dose of 250U.<<<
I don't understand. Doesn't the value lie in the treatment efficacy and duration regardless of the dose size?
A doctor or patient wouldn't base their treatment decision on the size of the dose compared to the size of dose of the competition....would they?
FGEN > FibroGen to present efficacy, safety analyses from Roxadustat Phase 3 Program
https://thefly.com/landingPageNews.php?id=3174772&headline=FGEN;AZN;ALPMY-FibroGen-to-present-efficacy-safety-analyses-from-Roxadustat-Phase--Program
FibroGen, Inc. (FGEN) and its partners, AstraZeneca (AZN) and Astellas Pharma Inc. (ALPMY), will present new analyses from the global Phase 3 program at the upcoming American Society of Nephrology Kidney Week 2020 Reimagined, assessing the potential of roxadustat, a first-in-class orally-administered hypoxia-inducible factor prolyl hydroxylase inhibitor, to revolutionize the treatment of anemia in patients with chronic kidney disease. The virtual congress will take place October 22-25, 2020. FibroGen and its partners will present 42 abstracts, including 2 late-breaker poster presentations, and 10 which have been accepted for oral presentation. Twenty-eight presentations on roxadustat for the treatment of anemia associated with CKD will further demonstrate the depth and breadth of the roxadustat global Phase 3 development program and build on the known clinical profile of roxadustat in treating a broad spectrum of CKD patients. Another 12 presentations on CKD anemia epidemiology and disease state outline the burden of anemia on CKD patients and their unmet medical need for innovative therapies. In addition, two late-breaking poster presentations will explore associations between cardiovascular safety and hemoglobin levels achieved with roxadustat in both non-dialysis-dependent and dialysis-dependent CKD patients. "Our roxadustat clinical data at ASN Kidney Week 2020 Reimagined demonstrate consistent efficacy and positive safety results across the continuum of chronic kidney disease patients with anemia, adding to the established body of evidence highlighting roxadustat as a potential foundational treatment for this condition affecting millions of patients," said Enrique Conterno, Chief Executive Officer, FibroGen. "We thank the investigators, study site staff, and patients who participated in the global roxadustat development program."
Read more at:
https://thefly.com/n.php?id=3174772
RVNC > Revance Reports Positive Results from ASPEN-1 Phase 3 Trial of DaxibotulinumtoxinA for Injection in Cervical Dystonia
https://investors.revance.com/news-releases/news-release-details/revance-reports-positive-results-aspen-1-phase-3-trial
- Trial met primary and all secondary endpoints for both 125- and 250-Unit doses with high statistical significance -
- DaxibotulinumtoxinA for Injection was effective and generally well-tolerated in reducing the signs and symptoms for cervical dystonia, delivering up to a median duration of 24 weeks -
- Results suggest DaxibotulinumtoxinA for Injection has the potential to reduce frequency of cervical dystonia treatments by up to 50% annually -
- Global market opportunity for cervical dystonia is $340M1 -