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Interesting sales estimates for Sota.
Apr 30, 2024
Leerink initiated coverage of Lexicon with an Outperform rating and $5 price target. The firm believes Lexicon’s first-in-class dual SGLT1/2 inhibitor sotagliflozin could address unmet need across multiple indications with large market opportunities, including heart failure, hypertrophic cardiomyopathy and Type 1 diabetes with chronic kidney disease, which could collectively drive blockbuster sales. Inpefa’s U.S. launch in HF should benefit from several meaningful tailwinds, Leerink says. It forecasts peak U.S. sales of $1B for Inpefa in HF and peak U.S. sales of $325M for sotagliflozin in HCM in FY32. The firm also points out that Lexicon plans to resubmit Zynquista’s NDA filing by mid-2024, with an anticipated 6-month review. Leerink forecasts peak U.S. sales of $225M for Zynquista in T1D with CKD in FY32.
A new corporate presentation has been issued. It has updated clinical data with Tus/Ven doublet obtained in 60 evaluable patients. Previous analysis presented at ASH was done in 36 patients. Interesting, they show only waterfall plot on slide 16, no tables with all nuances. I manually counted all CRc there and ended up with number 11. So, it gives a CRc rate of 11/60, or 18%. In ASH presentation it was 9/36, or 25%. I think 18% is too low for evaluable population. Looks like Tus is not so powerful drug to be used as a single agent or in combination with Ven in R/R patients. Therefore, Aptose has no other choice but to run a triplet trial hoping for more favorable results.
Titles of olutasidenib presentations at ASCO:
1. Safety and efficacy of olutasidenib treatment in elderly patients with relapsed/refractory mIDH1 acute myeloid leukemia.
2. Patients with relapsed/refractory mIDH1 AML who proceeded to transplant after olutasidenib treatment.
3. Olutasidenib for mutated IDH1 acute myeloid leukemia: Final five-year results from the phase 2 pivotal cohort.
Title of the second abstract, "Phase 1 study of BDTX-1535, an oral 4th generation covalent EGFR inhibitor, in patients with recurrent glioblastoma: Preliminary dose escalation results".
Titles of ASCO presentations are available.
Here is a title of BDTX-1535 presentation, "A phase 0/1 trigger trial of BDTX-1535 in patients with recurrent high-grade glioma (HGG) with EGFR alterations or fusions".
From today's presentation.
We don’t need to demonstrate activity on any single non-classical mutation to get a broad label. We need to cover a few mutations across certain subcategories of no-classical mutations shown in AACR presentation. These subcategories include L858R+non-classical, classical-like, PACC alone and complex, other non-classical, ecto- and juxtamembrane domain mutations.
The prevalence of non-classical EGFR mutations is approximately four times higher than that of EGFR Exon 20 insertions.
On Monday, Wedbush, a financial services firm, increased its price target for Black Diamond Therapeutics (NASDAQ:BDTX) shares to $16.00, rising from the previous target of $10.00. The firm has maintained an Outperform rating on the stock.
This adjustment follows Black Diamond's presentation at the American Association for Cancer Research (AACR) which highlighted the potential market for its drug candidate BDTX-1535 in the treatment of non-classical EGFR mutations and osimertinib-resistance mutations in non-small cell lung cancer (NSCLC).
According to the analysis presented by Black Diamond, non-classical EGFR mutations are highly prevalent, found in 22-30% of first-line treatment-naïve EGFR-mutated NSCLC cases. This prevalence is approximately four times higher than that of EGFR Exon 20 insertions. The firm noted that patients with these non-classical mutations often have a poor response to existing EGFR inhibitors.
Additionally, the mutations, along with C797S, represent a significant mechanism of resistance to current EGFR inhibitors. Wedbush believes that BDTX-1535 could be a leading therapy for patients with non-classical and C797S mutations. The firm sees promising development opportunities for the drug in various treatment settings, including post-adjuvant, first-line (1L), and second-line (2L) post-osimertinib.
Black Diamond Therapeutics has recently begun a Phase 2 cohort study of BDTX-1535 in a first-line treatment setting following feedback from the FDA, with initial data expected in 2025.
The company is also anticipating Phase 2 data from second and third-line (2L/3L) cohorts for patients with C797S and/or non-classical mutations, and non-classical mutations alone, which are expected to be released in the third quarter of 2024.
https://www.investing.com/news/company-news/wedbush-raises-black-diamond-stock-target-on-drug-potential-93CH-3369858
Slides from AACR presentation are posted.
https://investors.blackdiamondtherapeutics.com/events-presentations#target-2
Look at slides 8-10. I counted more than 80 mutations on X-axis. Great contribution from Heymach lab, a lot of work. Most important is that BDTX-1535 works for all of them with minimal effect on wild type EGFR (slide 10). Although it is preclinical data, even not in mouse experiments, the drug shows strong antiproliferative effect and differentiated profile. Waiting for GBM data in 2ndQ and more clinical data in EGFRmut NSCLC in 3dQ.
Just published, "Olutasidenib in post-venetoclax patients with mutant isocitrate dehydrogenase 1 (mIDH1) acute myeloid leukemia (AML)". The results of this phase 2 study support data from registrational cohort demonstrating that Olutasidenib works well in patients previously treated with venetoclax.
https://pubmed.ncbi.nlm.nih.gov/38538632/
20% probability of success
Published 03/27/2024, 05:28 PM
On Wednesday, Jones Trading adjusted its outlook on Aptose Biosciences (NASDAQ:APTO), lowering the price target to $5 from the previous $12, while maintaining a Buy rating on the company's stock. The adjustment comes as Aptose Biosciences shifts its development focus towards a new drug combination for treating Acute Myeloid Leukemia (AML).
The firm highlighted that Aptose's immediate strategy will concentrate on a triplet combination therapy involving tuspetinib, venetoclax, and HMA for first-line AML treatment. A pilot study for this combination is slated to begin in the summer, with initial findings expected to be presented at the American Society of Hematology (ASH) conference.
Meanwhile, the development for relapsed/refractory AML has been paused to improve strategic positioning, with data to be shared at the European Hematology Association (EHA) 2024 conference.
Jones Trading noted that if Aptose demonstrates clear clinical benefits in the first-line setting, it may lead to enhanced business development opportunities as compared to the relapsed/refractory AML setting. Still, the firm also pointed out that a capital overhang is a significant pressure point for both the stock and its clinical development progress.
The company's current cash position stands at $18.6 million, which is expected to fund operations through August 2024. Jones Trading has updated its financial model to reflect the new strategic direction towards first-line AML treatment, estimating unadjusted peak sales of approximately $250 million, assuming a 20% probability of success and a 40% market penetration among patients unfit for intensive chemotherapy.
In light of these developments and other minor changes across the model, Jones Trading reiterated its Buy rating but reduced the price target for Aptose Biosciences to $5. The firm believes that despite the lowered target, the company's stock remains a positive investment opportunity.
https://www.investing.com/news/company-news/aptose-biosciences-target-cut-maintains-buy-rating-on-new-drug-development-93CH-3355850
Not sure that increase in plasma concentration from 1 uM to 2-3 uM will help much. They don't report responses in 11 new AML patients they studied. Most disappointing is that they stopped developing Tus/Ven doublet as potentially registrational combination. They have good data with Flt3mut patients and now instead of working in this direction, they offer you to focus on triple combination project for which they don't have any preliminary data. A lousy strategy and Rice is a lousy leader.
Good read on Olutasidenib
https://journals.lww.com/oncology-times/fulltext/2024/03000/olutasidenib_as_a_breakthrough_for_r_r_midh1_aml.25.aspx
Important further research: 1) studying whether olutasidenib can eliminate the stem cell fraction within each patient's IDH1-mutant AML; 2) characterization of synthetic lethality involving olutasidenib in IDH1-mutant AML.
Here is what Bejar said at ASH in December, “Brisk patient enrollment in our APTIVATE trial has led to a fast-growing database that includes many more patients at various stages of treatment. We look forward to reporting our next set of data in the first quarter of 2024.” I think, it should happen at earing call. Last chance to impress investors?
Rolvedon pediatric study is a postmarketing requirement from FDA. If it was up to Spectrum, they wouldn’t run it because of small commercial opportunity and approved Neulasta. I think completion of Phase 2 is what ASRT needs to accomplish. I doubt phase 3 will be required but they need to complete current study and to show the results to FDA that can happen 3-4 years away from now. As for Neulasta you can find that “no overall differences in safety were identified between adult and pediatric patients based on postmarketing surveillance”. As for same day dosing, I think, nobody knows what the next step looks like. Depends on data. Three years ago, JT said “If data is good, we would engage in a discussion with the FDA to path forward”. About a year ago, TR said the same, “whether that be going to chat with FDA about a regulatory path forward, whether it is publication, it is really contingent upon what we see in that data”.
Lexicon will resubmit an NDA for sotagliflozin for patients with type 1 diabetes and chronic kidney disease. Good news. FDA rejected an NDA for type 1 diabetes in 2019. Now they changed their mind but only for patients with T1D+CKD. According to today's company presentation, slide 10, this population makes 21% of adults with T1D, or ~357,000 patients. Not a big addition to current indication. However, it will be the first gliflozin approved for T1D. No competition.
Listened to Mark Velleca at Cowen Health Care Conference. One question to him was "What BDTX-1535 success looks like?" He said, in 2nd/3d line, ORR of 30%+ and mDoR of 6 mo. In 1st line with non-classical mutations, ORR of 50%+ and mDoR of 12 mo.
Expect GBM data at ASCO in June. As I understand, they will present data from phase 1 study where GBM is a separate cohort and from the second early phase 1 GBM study, called "Window of opportunity" where treatment is first line, EGFR status is confirmed and concentration of drug in tumor was measured. Second trial will provide more valuable information. If positive, BDTX will initiate a registrational trial in first line patients.
It helps to understand why 1535 is a good drug after Osimertinib and why you may want to use it instead of Osimertinib in first line.
BDTX-1535 abstract for AACR presentation is released. There is no clinical data, it is about science. This study was conducted mostly by scientists from MD Anderson Cancer Center including John Heymach, who is an expert in EGFR/HER2 mutations in NSCLC. They discovered that treatment of two classical EGFR mutations, Exon 19 deletions and L858R, by Osimertinib results in two different resistance outcomes. Patients with Exon 19 deletions usually develop C797S resistance mutation whereas patients with L858R develop multiple non-classical resistance mutations. They also found that non-classical mutations often co-exist with L858R in first-line patients, making Osimertinib treatment less effective. For these patients BDTX-1535 should be a better option.
https://www.abstractsonline.com/pp8/#!/20272/presentation/8874
Good to know, "if all goes well the drug could move into phase 3 in 2025, and hit the market in 2027".
https://www.pharmavoice.com/news/black-diamond-cancer-mutations-market-approval/709074/
I don’t have an answer about what does it mean. I can explain why they will finish it earlier. Because they reduced the number of patients from 90 to 50. Good sign is that trial is still enrolling. It means they think that a positive outcome is still possible. What is next if the data is good? In my opinion, for approval they need to conduct a larger trial. Not sure if they want it.
So far, I like what I see. 1535 has a nice PK profile and it definitely has activity for non-classical mutations and C797S. Therefore, it potentially has a place in the market for post Osimertinib patients. First line non-classical also looks reasonably promising. I am not sure about GBM. Their “Window of Opportunity” trial is unusual by design. I've never heard of other drugs being tested that way, but I guess it is the only way to get a clear answer. We’ll see the data at ASCO. If positive, the company will be in a unique position to address unmet medical needs of patients with EGFR mutated GBM. Cannot say much about their second drug, BDTX-4933. Pre-clinical data looks good, but I won’t speculate on drug activity until I see at least early clinical data.
Cannot post. Something is wrong with iHUB.
Good read on BDTX-1535 and EGFR mutations. Expect some data at AACR in April and ASCO in June. Note, "As such he’s happy to accept that BDTX-1535 has no activity on T790m". It is what I suspected reading and listening to last year company presentations. But it is OK with me. Drug looks good for non-classical and C797S mutations.
https://www.oncologypipeline.com/apexonco/black-diamond-picks-its-lung-cancer-battle
Rigel Pharmaceuticals Acquires U.S. Rights to GAVRETO®
FEBRUARY 22, 2024 7:50AM EST
GAVRETO® (pralsetinib) is an FDA approved targeted therapy for the treatment of RET fusion-positive metastatic non-small cell lung cancer and advanced or metastatic thyroid cancer
Acquisition of established U.S. marketed product further expands Rigel's portfolio and leverages Rigel's existing infrastructure in both the institutional and community settings
GAVRETO generated ~$28M in U.S. net product sales in 2023
Hanmi Pharma said it has signed a strategic agreement with its U.S. partner company, Assertio Holdings, which previously acquired Spectrum Pharmaceuticals, to re-acquire the rights to Rolontis, a long-acting neutropenia treatment and Korea's 33rd novel drug, for the Asian and African markets.
Published 2024.02.02
?? : KBR(https://www.koreabiomed.com)
Some thoughts on Rice.
Rice has an interesting career. “He served as Head of the Laboratory of Antiviral Drug Mechanisms and Manager of the HIV Clinical Interface Laboratory for the National Cancer Institute (NCI), National Institutes of Health from 1992 to 1998. In this position, Dr. Rice directed the activities of several projects targeting new ways to treat HIV and other infectious diseases. From 1989 to 1992, he was professor of Pediatric Hematology and Oncology at Emory University School of Medicine, where he built a program to identify new molecular structures as antiviral targets”. So, he was in hematology/oncology, but it was not related to oncology. Then, from Aug 1998 to Aug 2003 he worked as a CEO of Achillion Pharmaceuticals, an anti-infective pharmaceutical company. Under his leadership no drug was approved. From 2003 to 2013 he served as a CEO of Cylene Pharmaceuticals. The company was working on oral CK2 protein kinase inhibitor, CX-4945, in patients with advanced solid tumors, or multiple myeloma. This drug is still in clinical trials, not even close to FDA approval. Their second drug was Quarfloxin, a selective binder for MYC GQ structure. Is it related to APTO-253? Anyway, later quarfloxin was discarded due to its poor bioavailability. Isn’t it a familiar theme? And from 2013 to the present, Rice has been a CEO of Lorus/Aptose Biosciences. The result of his work as a leader of Aptose is two failed drugs, APTO-253 and Luxeptinib. Point is that during his very long career in biotech industry as a CEO, Rice was not able to bring any drug to the market. I hope Tuspetinib is his last chance.
Would you like to share your greener pastures?
In recently posted Hanmi 2024 1Q IR presentation, you can see Tuspetinib data on slide 18. Nothing new there but you have an impression that it is their own data. If Aptose needs a partner to start triplet in 1st line patients, Hanmi would be the best candidate.
https://www.hanmipharm.com/file/admin/ir/1707107587558.pdf
It looks like Aptose can replace their curent employees with Koreans and Hanmi will pay them salary, bonuses etc. Is it a kind of takeover? Let's start from Rice.
From latest 8-K. Very interesting. What is a Hanmi's purpose?
"Hanmi will have the right to designate for employment one or more individuals that are legally able to work in the United States or Canada (each, an “Hanmi Nominee”) to a position or positions within Aptose in applicable areas based on each Hanmi Nominee’s skills, education and experience. The parties agreed that the Hanmi Nominee shall be subject to Aptose’s usual employment rules, practices, policies, evaluation procedures, as amended from time to time and Aptose shall retain the right, in its sole discretion, to terminate such Hanmi Nominee’s appointment with Aptose for violations of Aptose’s employment rules, practices, policies and procedures. The parties also agreed that the Hanmi Nominee shall be entitled to salary, bonus, vacation, incentive payments and bonuses, expenses, allowances and any applicable benefits in amounts and to the extent consistent with employees of Aptose serving or having recently served in a similar capacity with Aptose with such amounts to be reimbursed to Aptose by Hanmi. In the event that a visa or other permit is required to be obtained to permit the Hanmi Nominee to work in the United States or Canada the parties agreed that Aptose would use its commercially reasonable efforts to assist the Hanmi Nominee with obtaining such visa or permit. The parties agreed that upon the nomination of the Hanmi Nominee that the parties would enter into a separate service agreement to outline the specific terms and conditions of the Hanmi Nominee’s appointment".
On page 7 under Key findings: "We are seeking a collaboration partner to study TUS as part of a TUS/VEN/HMA triplet in 1L newly diagnosed AML patients unfit for chemotherapy with or without FLT3 mutations".
"We expect to revise our current development as follows. Assuming the net proceeds from this offering and our existing cash, cash equivalents and short-term investments, a net proceeds from the concurrent private placement offering, a committed equity facility, and ATM we plan to, (i) complete our ongoing APTIVATE clinical trial studying TUS and TUS/VEN, (ii) pause enrollment in the LUX G3 study and (iii) evaluate other costs reductions in general and administrative expenses."
Not a word about registrational trial?
A short video with Akriti Jain, MD, describing Tuspetinib data. She is particularly excited about effect of Tusp in Flt3mut patients.
https://www.healio.com/news/hematology-oncology/20240118/video-promising-monotherapy-treatment-for-challenging-to-treat-aml
From 3rdQ earning call, "Extension into HR-MDS and CMML planned: 4Q2023". Will they announce it today or tomorrow?
What is interesting, Coherus said their injector is more patient friendly than what is used in Onpro. So, it looks like a competition of injectors now. Is it possible to win Neulasta market by introducing a better injector? Unexpected twist.
Shares of Coherus BioSciences (NASDAQ:CHRS) surged 36.4% after the FDA had approved an on-body injector version of the biosimilar – Udenyca for post-chemotherapy treatment Neulasta.
https://seekingalpha.com/news/4050413-biggest-stock-movers-today-coherus-biosciences-bit-digital
It will make more difficult for Rolvedon to compete. Why Spectrum or Assertio didn't start on-body injector program in addition to same day dosing?
December corporate presentation posted. Most important info is on slide 26, "$10M financing combined with the $4M 2nd tranche from Hanmi extends cash runway to the end of Q3/2024 and delivers data from TUS/VEN Doublet in AML by 2Q/2024". This slide shows that they are still planning to initiate an MDS trial in 2023. Good luck. They have three days left to accomplish it. And of course, a delay. Now TUS/VEN/HMA triplet pilot arm for 1L AML will start in 2ndQ24. In ESH presentation, it was end of 2023. Slide 5 shows CR rate for patients with prior-VEN failures demonstrated in other studies. In one study, it was 15%, almost same as for TUS/VEN combination in Flt3 WT patients. It is important, since they need to establish and negotiate with FDA a certain CR rate to beat in pivotal study.
Hi ATLcitizen! Good to see you here. I think physicians view Ryzneuta the same way as Rolvedon. No clear differentiation from Neulasta. Assertio should work on same day dosing. As for Poziotinib, I don't know. I don't see any new trials with Pozi but I see several drug candidates in development that are less toxic. I found interesting document describing what exactly Spectrum did to be acquired. It looks like Hanmi was considering to buy Spectrum.
https://www.sec.gov/Archives/edgar/data/1808665/000110465923071264/tm2315184-6_s4a.htm
This acquisition story is described on pp71-82 step by step. Board was interested to sell the company when TR became a CEO. "Following the appointment of Thomas J. Riga as Spectrum’s President and Chief Executive Officer effective January 1, 2022, the Spectrum board of directors engaged in discussions regarding potential strategic alternatives at each of its regularly scheduled meetings and authorized Mr. Riga and the Spectrum management team to explore potential strategic alternatives".
I don't know. My guess is G3 formulation is not good enough. Otherwise they would deliver good news.