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ADMIRAL trial was Gilteritinib against salvage therapy in r/r AML patients with Flt3 mutations. Several salvage regimens are available. I guess, they can be used as a control arm in Tusp mono trial.
Spectrum Pharmaceuticals Has Been Awarded A Five Year Veterans Affairs Federal Supply Schedule Contract Initially Worth $23M
https://www.benzinga.com/general/biotech/23/03/31534829/spectrum-pharmaceuticals-has-been-awarded-a-five-year-veterans-affairs-federal-supply-schedule-co
6505--Spectrum Pharmaceuticals, Inc. Contract Award 4/15/2023 to 4/14/2028 Spectrum Pharmaceuticals
https://sam.gov/opp/b7421fb148904a81970ef3440ec2c235/view
Canaccord Genuity has decided to maintain its Buy rating of Aptose Biosciences (NASDAQ:APTO) and lower its price target from $13.00 to $8.00.
Who wouldn't be happy with $8/share?
https://markets.businessinsider.com/news/stocks/canaccord-genuity-maintains-buy-rating-for-aptose-biosciences-here-s-what-you-need-to-know-1032194902
My guess, if data is good, they will need to run ph2/3 study for approval. On the other hand, they might choose just to publish data without pursuing approval. In this case physicians can use same day regimen off label.
Following the latest results, Spectrum Pharmaceuticals' five analysts are now forecasting revenues of US$50.6m in 2023. The loss per share is expected to greatly reduce in the near future, narrowing 46% to US$0.21.
https://finance.yahoo.com/news/earnings-spectrum-pharmaceuticals-inc-nasdaq-141328127.html
It should affect Aptose. After that, don't think FDA will allow them to run a single arm combo trial. Possibly, even Tusp single arm monotherapy trial is in question.
Mar 24, 2023
US FDA proposes higher bar for accelerated approvals for cancer drugs.
Accelerated approvals allow the agency to move therapies that target serious and life-threatening conditions to the market more quickly but have been criticized because some drugs have later been proven to be ineffective.
The FDA proposed that companies conduct randomized controlled trials in which patients receive either a therapy or another alternate treatment instead of trials that test the drug without a comparator, known as single-arm studies.
Single-arm studies can be conducted in some cases, but those need to be discussed with the agency beforehand, it said.
"Given the limitations of single-arm trials, a randomized controlled trial is the preferred approach to support an application for accelerated approval," the FDA said.
https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-seeks-more-rigorous-trials-cancer-drugs-accelerated-nod-2023-03-24/
I don't think it was disclosed by Spectrum or Hanmi. I know that gross profit margin for Udenica, a biosimilar of Neulasta, was higher than 90% a few years ago.
Yes, unless they want to recruit Ven-naive patients. But if I heard it correctly, they are planing to negotiate a single-arm Tusp/Ven trial for accelerated approval. Therefore, it is absolutely critical what FDA wants to see, ORR and mDoR should be pre-determined.
As I previosly mentioned, Tusp/Ven trial won't be very informative since they will compare Tusp/Ven with Tusp, not with Ven. Contribution of Tusp in combo will be unclear.
Was distracted yesterday by multiple tasks and could not clearly follow their story about RAS patients. Therefore, disregard my two latest posts. Getting older, I guess.
I was confused about 29% CR/CRh response rate and 42% ORR in patients with RAS mutations. I don’t remember they reported these numbers before. Slide 33 in their January presentation shows ORR of 38% in 3 out of 8 patients and CR/CRh RR of 25% in 2/8 patients with RAS mutations. As I can see, the trick is in reduction of denominator. If they have 7 patients instead of 8, ORR is 3/7, or 42% and CR/CRh RR is 2/7 or 29%, the numbers they reported yesterday. Great way to improve efficacy. Same story was with CR/CRh RR in p53mut patients.
I think, most revealing in yesterday call was a mention of interest from big pharma. I hope it is not about providing Venetoclax with no cost. I hope it is about buyout. I don’t see Aptose moving multiple Tusp programs forward. Maybe they should sell Tusp and focus on Lux.
OK, they said they treated 60 patients. Closest to 0.29 numbers are 17/60=0.28 and 18/60=0.3 It is either 28% or 30%.
I had no chance to listen to the call yet, but from what I am reading, how it is possible to have a 29% CR/CRh response rate in patients with RAS mutations? You should have 29 responders with RAS mutations out of 100 patients. No more, no less. Have they already enrolled 100 patients?
Mar. 23, 2023, 10:15 AM
Jefferies analyst Maury Raycroft maintained a Buy rating on Spectrum Pharmaceuticals (SPPI – Research Report) yesterday and set a price target of $3.50. The company’s shares opened today at $0.73.
In today's earning call, Tom said that they are going to present data from a same-day Rolvedon trial in 2H23. It is what their R&D department is working on now, besides pediatric study. I was hoping to hear about their future pipeline but nothing was said. Looks like Rolvedon sales in 1Q23 will be OK. J-code will be in force from April 1.
Just published, "Poziotinib in Treatment-Naïve Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-label Phase 2 Trial (Cohort 4)" by many authors including Heymach, Lebel and Socinski.
Good article. A lot of positive data but at the end you can find "The ZENITH20 study was terminated due to an FDA decision".
https://www.jto.org/article/S1556-0864(23)00199-5/fulltext
Another Heymach study with poziotinib will be presented at AACR, "Role of individual HER family members and pan-HER targeting treatment strategy in NRG1 fusion positive cancer".
From the abstract.
NRG1 gene fusions are rare, clinically actionable somatic alterations identified in 0.1% of all tumors. Previous studies have demonstrated that NRG1 fusions signal through ERBB/HER family members and that HER2 inhibition has anti-tumor activity in NRG1 fusion-driven cancers. However, NRG1 can also bind to HER4 in addition to HER3, and the contribution of individual HER family members in tumor cells with NRG1 fusions has not been fully elucidated.
Our data indicated that pan-HER tyrosine kinase inhibitors (TKIs), such as poziotinib, were more effective at blocking HER2/HER3, EGFR/HER3 and HER4 signaling in NRG1-fusion expressing cells as compared to TKIs with greater relative specificity for EGFR (erlotinib, lapatinib), HER2 (pyrotinib), EGFR/HER2 (afatinib, dacomitinib, neratinib) or HER2/HER4 (TAS0728,tucatinib).
https://www.abstractsonline.com/pp8/#!/10828/presentation/6748
New poziotinib data will be presented at AACR 2023 meeting by Heymach group. Abstract title: "Trastuzumab deruxtecan resistance is associated with reduced responsiveness to topoisomerase inhibitors (payload resistance) but no reduction in sensitivity to HER2 tyrosine kinase inhibitors''. They demonstrated that poziotinib may retain anti-tumor cell activity in HER2 mutant tumor cells with acquired resistance to HER2 ADCs such as Enhertu.
https://www.abstractsonline.com/pp8/#!/10828/presentation/9193
According to most recent corporate presentation, it should occur in Q1 2023:
EOP1 Meeting with FDA to establish response rates for accelerated approval as monotherapy for R/R AML/ Prior FLT3i failure and
to set stage for triplet trials.
Since APTO earning call is on Mar 23, 2023, most likely they will tell us about the outcome of this meeting.
Cara, Iovance, and Karyopharm among biotechs with no exposure to SVB.
https://seekingalpha.com/news/3946617-iovance-allogene-and-karyopharm-among-biotechs-with-no-exposure-to-svb
This news will dominate short term. Even biotech companies with no exposure to SVB will be affected.
https://www.bloomberg.com/news/articles/2023-03-10/svb-sivb-collapse-brings-another-blow-to-cash-starved-biotech-industry
Lux is a BTK inhibitor because it inhibits BTK. Lux is a Flt3 inhibitor because it inhibits Flt3. Lux is a multi-kinase inhibitor because it inhibits other kinases including BTK and Flt3. You can call it by one of these names, it depends on context of conversation. Same with Tusp. I don't see any problems with that.
"You need to get past thinking about the proteins as Flt3 inhibitors or BTK inhibitors. Those functions are subsets of their activities".
Don't understand. Proteins as inhibitors? Which functions? Activities of proteins or inhibitors?
New Lux paper is out, "Luxeptinib interferes with LYN-mediated activation of SYK and modulates BCR signaling in lymphoma" with Rice as co-author. They are saying that "in human lymphoma cells LUX and Ibrutinib (IB) have quite distinct mechanistic effects on the phosphorylation of BTK and its activity, and on the upstream kinases SYK and LYN, and the adaptor protein BLNK against which LUX is very potent and IB had little effect".
And "The results reported here are important because, in combination with evidence that LUX inhibits TLR signaling and activation of the NLRP3 inflammasome at concentrations well below those attained in patients, they indicate that LUX as a unique kinase profile quite different from that of IB and suggest that LUX may have activity against autoimmune and inflammatory diseases of multiple types in addition to lymphomas".
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0277003
It looks like a driver mutation is in Flt3. Therefore, any Flt3 inhibitor can be used. Not sure what is the advantage of using multi-kinase inhibitors in this case.
Spectrum updated pipeline on corporate website. They removed all cohorts of Zenith-20 trial, except one, Previously treated HER2 exon 20 insertion mutation positive NSCLC. Why didn't they remove this one?
Next news from APTO is the results of EOP1 meeting with FDA which could possibly already happened. Wonder what ORR and DoR in registrational trial is needed.
I checked again Tuspetinib on Clinicaltrials.gov. It says "Venetoclax will be given to patients in combo treatment group (Part C) either in 50 mg or 100 mg tablets". Not sure whether they are distinct doses or just dose increments.
https://clinicaltrials.gov/ct2/show/NCT03850574?term=aptose&draw=2&rank=4
They said results in 2H2023. As of Jan 2023, 28 patients were enrolled and they are in the midst of dose-escalation part of the trial.
Interesting presentation by David Epstein at Cowen today. He said that Osimertinib currently is not used in 2nd line setting, only in 1st line. What does it mean for 2nd line post Osimertinib therapy? It means simply a loss of T790M mutation. And they don’t see T790M patients in BDTX-1535 Ph1 trial. What they do see is Osi-resistance mutations, like C797S. They also see a whole family of mutations in EGFR that occur on a backbone of a primary driver mutations. Therefore, high unmet medical need in 2nd line setting. This observation has been overlooked by virtually every company developing 4th generation EGFR inhibitors.
They are testing 50 mg and 100 mg of Venetoclax with Tusp starting at 80 mg. Are you still following BDTX? Today they made an interesting presentation.
As I remember, Venetoclax by itself is associated with myelosupression. Why do you think in combo it will be different?
Good news for Karyopharm.
Incyte ending phase 3 program evaluating myelofibrosis candidate parsaclisib.
Incyte (NASDAQ:INCY) said it would end a phase 3 program examining its myelofibrosis candidate parsaclisib with Jakafi (ruxolitinib) after an interim analysis showed the study was unlikely to meet its primary endpoint.
https://seekingalpha.com/news/3944167-incyte-ending-phase-3-program-evaluating-myelofibrosis-candidate-parsaclisib
I have a few.
Korean analyst on Rolvedon
Published 2023.03.03 18:33
Hanmi Pharm's R&D prowess is also being proven in the U.S. with Rolvedon.
Rolvedon is Hanmi's first new biologic drug that is used to treat or prevent severe neutropenia in cancer patients who have undergone chemotherapy.
The drug is the first product to receive marketing approval by applying Hanmi's proprietary platform technology, "LAPSCOVERY," which boosts a bio-medicine's efficacy.
Hanmi had previously licensed out the treatment to Spectrum Pharmaceuticals, its U.S. partner, in 2012, and Spectrum received approval in September of last year.
Notably, there is additional hype surrounding the success of Rolvedon as it recently got listed on the U.S. public insurance reimbursement drug list.
Industry watchers expect that the listing will have a positive impact on expanding prescriptions and establishing brand awareness as the cost burden of patients is lowered.
Local analysts also expect good performance from Rolvedon this year.
"Spectrum estimation Rolvedon's sales in the fourth quarter of last year was $10 million," said Ha Hyeon-soo, an analyst at Yuanta Securities. "The drug's sales target this year is $100 million as the top three community oncology networks in the U.S. started using Rolvedon, and the three communities account for about 22 percent of the total clinic market."
https://www.koreabiomed.com/news/articleView.html?idxno=20574
However, in January, Reuters found an even higher median annual price of $193,900 for 17 novel drugs the FDA has approved since July 2022, paced by the $3.5 million list price of CSL’s Hemgenix®, the first and only FDA-approved gene therapy for hemophilia B and the most expensive drug ever sold (to date).
But Reuters acknowledged the median had fallen from $257,000 in the first half of 2022, thanks to five drugs marketed with five-figure list prices, the lowest being Spectrum Pharmaceuticals’ Rolvedon™, an infection-fighting drug in adults with non-myeloid malignancies, whose price the news agency pegged at $27,000 based on wholesaler information.
https://www.genengnews.com/gen-edge/the-unbearable-cost-of-drug-development-deloitte-report-shows-15-jump-in-rd-to-2-3-billion/
$100M this year, how about that?
US sales of Hanmi Pharmaceutical Co.’s Rolvedon (eflapegrastim-xnst), a drug used to reduce the incidence of infection as manifested by febrile neutropenia in adult patients with non-myeloid malignancies, topped $10 million just three months after its launch in the US by Spectrum Pharmaceuticals Inc. The US partner projected its sales would reach $100 million this year.
https://www.kedglobal.com/bio-pharma/newsView/ked202302270012
Here is a what Harry Erba, a hematologic oncologist from Duke thinks about Tusp data presented at ASH last year (started from 12 min). Interesting comment on TKIs in CML. He said it is not clear what is better, a more targeted kinase inhibitor or a less targeted kinase inhibitor that is able to overcome resistance pathways.
https://www.onclive.com/view/acute-myeloid-leukemia-updates-from-the-ash-2022-annual-meeting
You need to consider combo(s) in first line and other patient populations for which we don't have any data yet.
Aptose own estimates for Tusp US sales potential in 2035, FLT3(+) RR AML / Prior FLT3i (Gilt) - $25M, FLT3(WT) RR AML - $55M. It doesn't include combo in first line and maintenance.
The abbreviation of millions is now 'mn' instead of 'm'. One of the main reasons is to benefit text-to-speech software, which reads out the 'm' as metres instead of millions, confusing visually impaired readers. It also comes into line with our style for billion (bn) and trillion (tn). Feb 4, 2022