Black Diamond Therapeutics Inc (BDTX) Quote

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".

BDTX under $10

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.

We’ve got a winner 🫡

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.

BDTX under $10

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.

Is this GBM data readout in April potentially needle moving? I.e if the partial response rate is high enough does it imply 1535 can really help with GBM or does the nature of the P1 level mean we can’t read that much into it

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.

Is this suppose to be a good thing?

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

Thanks for the response. I agree 1535 looks promising. I plan to follow it closely. I am also interested in their RAF inhibitor (4933). I follow VSTM very closely. They are focused on RAS pathway inhibitors. Both VSTM and IKNA have RAF/MEK clamps in trials. VSTM is in the lead. It will be interesting to see how BDTX positions 4933 in the context of current RAF inhibitors and these new clamps.

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/

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.

Thanks for the link. Interesting. What's your current opinion of BDTX? TIA.

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

The stock has been heating up the past couple of weeks… it seems like the data readouts for 1535 since the latest equity raise have been positive, and the new CEO had real success getting FDA approval at CGI before selling to Gilead and later taking G1 to Phase 3 and an IPO. This guy seems to have robust (dare i say overqualified) commercialization experience for a tiny biotech with promising P1 assets for solidly sized patient populations with unmet needs— either I’m missing something here, or the stock trading below their latest funding valuation is a pretty attractive entry price no? I’ve been seriously looking into it and have appreciated reading through @dcaf and @Fact Checkers posts on here thanks guys

Listened to yesterday fireside chat of Mark Velleca with Stifel analyst. It was first public appearance of Mark as a CEO of BDTX. I like how he answered analyst questions. He gave a clue to what we might expect from GBM part of BDTX-1535 study. He said that opportunity is in newly diagnosed patients where EGFR could be the major driver. My interpretation is that 1535 alone does not work well in recurrent GBM. However, combination of 1535 with Temozolamide in newly diagnosed GBM might work. He also talked a few minutes on a new study with BDTX-4933. Interestingly, he called this drug a Ras clamp. It clamps Ras in inactive conformation.

From BB Biotech (BION), a Switzerland-based investment company,
"Notable recent transactions include an addition to the company’s holding in Black Diamond Therapeutics, a targeted oncology player. Promising clinical data on BDTX-1535, a treatment for lung cancer, allowed Black Diamond to undertake a capital raising. BION made an additional investment to maintain its 15% ownership stake in the company. Exposure to Black Diamond was raised further via open market transactions. The managers like this company in part due to its deployment of massive computational power and machine learning to deepen its understanding of disease processes and speed up the identification and development of new treatments".
https://www.edisongroup.com/research/a-cutting-edge-sector-and-a-high-dividend/32799/

Correction, for $2.3/share.

Biotech Growth bought 400,000 shares of BDTX for $2.3M.
https://investors.blackdiamondtherapeutics.com/static-files/95be4946-8d92-41b8-a8e6-247129c9cd56

Oct. 16, 2023, 05:15 AM
Piper Sandler analyst Joseph Catanzaro maintained a Buy rating on Black Diamond Therapeutics (BDTX – Research Report) today and set a price target of $11.00.

Maybe more important, PK is considered as a biomarker that would potentially increase chances for remission in patients with highest levels of BDTX-1535 in tumor.

St. Joseph's Hospital and Medical Center in Phoenix is initiating a Phase 0 "Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants With EGFR Alterations or Fusions". The idea is to give patients BDTX-1535 prior to a planned resection. "During surgery, blood, tumor, and CSF samples will be collected to measure the amount of drug that is present in the samples. Participants with tumors demonstrating PK response will continue with once-daily BDTX-1535 treatment, continuously in 28-day cycles after surgery". Interesting. I guess it is the best way to study PK of drug in brain tumor.
https://classic.clinicaltrials.gov/ct2/show/NCT06072586?term=BDTX&draw=2&rank=3

It looks like some PRs are durable. Question is what is median duration of response?
https://s3.us-east-1.amazonaws.com/black-diamond-assets.investeddigital.com/files/2023_BDTX-1535_NSCLC_Phase_1_Clinical_Poster.pdf

BDTX: New article

Top of the list here: (10-12-2023)

https://www.stockilluminati.com/bdtx/news.php

Thanks dc,

I'm not sure if David resigned though, it sounded more to me that he was removed by the BOD.

Could it be possible that the BOD ousted Epstein on account of finding out about his relationship with PairX?.. and to the extent of licensing ip!!

https://www.pairxbio.com/post/duke-nus-spinout-pairx-bio-launches-with-strong-biotech-credentials-venture-capital-backing


"“I am delighted that Duke-NUS, Esco Ventures, Avendesora and the PairX founding team are partnering to commercialise our platform and pipeline of novel cancer antigen–T cell pairs. This seed financing uniquely positions PairX to advance precision immunotherapies designed to treat cancer patients defined by shared mRNA splicing defects,”
- Adj Assoc Prof Epstein

Theory: BOD saw this
https://www.biospectrumasia.com/news/54/16545/pairx-bio-launches-venture-capital-backing-targeting-cancer-immunotherapies.html
contacted David - "your fired".

(imo though, PairX is cutting edge in the TCR-T category and Epstein sees the future of this)

BDTX: Black Diamond Therapeutics to Present Preclinical and Clinical Data at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

https://finance.yahoo.com/news/black-diamond-therapeutics-present-preclinical-161400478.html

As I can see, David Epstein is a CEO of PairX Bio since Sep 2023. He is also a founder of this company. It can explain why did he leave BDTX.
https://www.linkedin.com/in/david-m-epstein-8836593/

I think, recent SP decline is related to three factors. 1. World Conference of Lung Cancer in September where several studies on drugs targeting EGFR mutations in lung cancer were presented, including 4th generation TKIs. It showed that market is relatively crowded. 2. Outcome of Janssen Landmark Phase 3 MARIPOSA Study where RYBREVANT plus lazertinib beat Osimertinib in 1st line EGFRmut NSCLC. It should affect BDTX strategy for 1535 development. Placing it post Osimertinib might became not so relevant. 3. CEO employment termination without cause.
Guess, all eyes are on data readout in GBM this quarter.

I don't think it is clinical data related, in this instance.

Done a bit of digging but need to verify some pieces of the puzzle.

Will send you a PM once i am sure of my dd.
( it's going to take me a while to check out a few things, limited time and swamped with my own work)

imo, this is not clinically related and believe BDTX is still on track with their excellent trials.

The replacement, Mark Valleca appears to be well experienced with medical development and the FDA.
This should bode well for BDTX as they move their clinical trials forward.

Without knowing why did it happened, I don't have clear opinion. But it could be either negative or neutral. I don't see how it can be positive. Hope, it is not clinical data related.

That is awesome information to have on this board DC. Thank you very much for that.

As i was thinking about the GBM criteria you outlined, it's a reasonable criteria standard, imo
The GBM patients biggest challenge is survivability so the PFS criteria makes sense, imo

What's your take on today's news regarding David Epstein's move out of the CEO position and replaced by Mark Valleca?

https://www.bizjournals.com/boston/news/2023/09/18/black-diamond-therapeutics-david-epstein-ceo.html?utm_source=sy&utm_medium=nsyp&utm_campaign=yh

Titles of BDTX presentations at triple meeting:
1. Oral presentation, Oct 8, 2023, "BDTX-1535, a CNS penetrant MasterKey inhibitor of common, uncommon and resistant EGFR mutations, demonstrates in vivo efficacy and has potential to treat osimertinib-resistant NSCLC with or without brain metastases".
2. Poster, "Pre-clinical evaluation of next-generation inhibitor targeting a wide spectrum of oncogenic BRAF dimers".
3. Poster, "Discovery and characterization of selective, FGFR1 sparing, inhibitors of FGFR2/3 oncogenic mutations for the treatment of cancers".

Listened to David Epstein presentation at Morgan Stanley Healthcare Conference two days ago. He said that measurement of clinical activity in GBM is more complicated than in NSCLC. It has to be done by RANO criteria, not by measuring ORR by Recist 1.1 criteria. They need to demonstrate increase in PFS and ultimately, in OS. Their goal is to achieve six months PFS in 25% patients. Possibly, it is a reason why they already reported NSCLC data but still waiting to release GBM data in 4thQ. Measuring PFS at 6 months takes longer then ORR.

BDPT....in @ 3.54......could see a technical bounce..... using tight stop loss.

BDTX: Company to present BDTX-1535 dose escalation data in NSCLC at the AACR-NCI-EORTC Conference in October 2023

https://www.stocktitan.net/news/BDTX/black-diamond-therapeutics-announces-first-patients-dosed-in-phase-1-is334cticxtl.html

https://www.aacr.org/meeting/aacr-nci-eortc-international-conference-on-molecular-targets-and-cancer-therapeutics-2/program/

Thank you for explaining that very well.
Today's BDTX news appears to confirm what you outlined .


https://www.stocktitan.net/news/BDTX/black-diamond-therapeutics-announces-first-patients-dosed-in-phase-1-is334cticxtl.html

September 11, 2023 - 8:00 am
Company to present BDTX-1535 dose escalation data in NSCLC at the AACR-NCI-EORTC Conference in October 2023

CAMBRIDGE, Mass. and NEW YORK, Sept. 11, 2023 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage precision oncology company developing therapies that target families of oncogenic mutations in patients with genetically defined cancers, today announced the first patients dosed in mutation matched expansion cohorts of non-small cell lung cancer (NSCLC) in the ongoing Phase 1 clinical study evaluating BDTX-1535.


BDTX-1535, a fourth-generation, brain-penetrant epidermal growth factor receptor (EGFR) MasterKey tyrosine kinase inhibitor (TKI), is under investigation for the treatment of NSCLC harboring intrinsic driver and/or acquired resistance (post-osimertinib) EGFR mutations and glioblastoma multiforme (GBM) with multiple EGFR alterations. The BDTX-1535 expansion cohort portion of the study will assess single-agent objective response rate (ORR) in a second- or third-line setting in NSCLC patients with EGFR intrinsic driver and/or acquired resistance mutations, who have received prior treatment with approved EGFR TKI.

The dosing of the first patients in the expansion cohorts follows the Company’s initial data readout from the dose escalation portion of the BDTX-1535 Phase 1 clinical study, which demonstrated clinical proof of activity through radiographic responses in NSCLC patients harboring diverse types of EGFR mutations including intrinsic driver and post-osimertinib acquired resistance EGFR mutations.

“The Phase 1 expansion cohorts will assess objective response rate and durability of response in NSCLC patients whose disease has progressed after prior EGFR inhibitor therapy, including prior osimertinib, and who have evidence of a variety of EGFR driver or resistance mutations that are targeted by BDTX-1535,” said Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond Therapeutics. “In conjunction with establishing an optimal dose for a future pivotal study, these efficacy data will be essential for establishing a regulatory pathway for BDTX-1535. Despite significant recent advances in treating lung cancer, there is a large unmet medical need for a targeted therapy for these EGFR mutation-positive NSCLC patients, for whom chemotherapy is still the most common treatment option.”

“Dosing of the first patients in the BDTX-1535 dose expansion cohorts represents an important step towards offering an oral therapeutic with manageable side effects as a potential alternative to chemotherapy-based regimens following progression on osimertinib for patients with treatment-resistant lung cancer,” said David Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. “The population of EGFR mutation-positive NSCLC is genetically heterogeneous – which has presented challenges in the development of effective therapies. BDTX-1535 was designed to disrupt the limited existing treatment paradigm by addressing real-world patterns of patient-specific EGFR mutations, and we remain focused on the rapid advancement of this novel MasterKey inhibitor.”

The discovery and development of BDTX-1535 was informed by the Company’s powerful Mutation-Allostery-Pharmacology (MAP) drug discovery engine, which leverages critical genomic profiling to expand the addressable patient population by targeting families of mutations with a single drug. Emergence of intrinsic driver and acquired resistance EGFR mutations to osimertinib represents a significant unmet need for patients with EGFR-mutant lung cancer. Thirteen percent of patients in the U.S. with EGFR mutation-positive NSCLC show presence of intrinsic driver mutations, which are associated with worse clinical outcomes when treated with currently approved EGFR TKIs. Fifteen percent of patients in the U.S. whose disease has progressed after osimertinib therapy show evidence of acquired resistance EGFR mutations (e.g., C797S) for which currently there is no approved EGFR TKI.

The Company is advancing BDTX-1535 as a potential targeted therapy option for patients with this broad spectrum of EGFR mutations in second-line NSCLC, and plans to investigate safety and efficacy in a first-line setting in NSCLC patients with intrinsic driver EGFR mutations after discussion with the U.S. Food and Drug Administration (FDA).

BDTX-1535 Phase 1 Clinical Study Design
The Phase 1 first-in-human, open-label clinical trial of BDTX-1535 (NCT05256290) consists of a dose escalation portion that evaluated the safety, pharmacokinetics (PK), and preliminary anti-tumor activity of BDTX-1535 followed by dose expansion cohorts. The trial is evaluating BDTX-1535 in patients with advanced/metastatic NSCLC harboring EGFR mutations with or without central nervous system (CNS) disease, or with recurrent GBM expressing EGFR alterations. The Phase 1 dose escalation portion of the study in NSCLC and GBM patients has been completed and the study is now progressing to evaluate BDTX-1535 as a single agent, second-line or third-line therapy in two cohorts of EGFR mutation-positive NSCLC patients with progressive disease after prior therapy with EGFR TKI (e.g., osimertinib) to assess ORR, CNS ORR, duration of response, and progression-free survival and further evaluate safety, tolerability and PK:

Second- or third-line NSCLC patients with acquired EGFR resistance mutations +/- CNS metastasis; and
Second- or third-line NSCLC patients with EGFR intrinsic driver mutations +/- CNS metastasis.
About Black Diamond Therapeutics
Black Diamond Therapeutics is a clinical-stage precision oncology medicine company focused on the development of therapies that target families of oncogenic mutations in clinically validated targets. Black Diamond leverages a deep understanding of cancer genetics and onco-protein structure and function, to discover and develop innovative therapies. The Company’s MasterKey therapies are designed to overcome resistance, minimize on-target, wild-type mediated toxicities, and be brain-penetrant to address significant unmet medical needs of patients with genetically defined cancers. The Company is advancing a robust pipeline with lead clinical-stage program BDTX-1535, targeting MasterKey mutations in both EGFR mutant-positive NSCLC and in GBM, and BDTX-4933, a program targeting RAF MasterKey mutations in solid tumors. For more information, please visit www.blackdiamondtherapeutics.com.

It is not easy to follow an evolving story of EGFR mutations in NSCLC and other cancers. Most common are mutations called the exon 19 deletions and exon 21 L858R mutation. Other mutations including exon 20 insertion mutations are less common. To treat patients with most common mutations, two drugs, Iressa and Tarceva were developed. BTW, David Epstein and Elizabeth Buck, were involved in the development of Tarceva. They know this field. Patients treated with Iressa or Tarceva sooner or later progress. One of the reasons for disease progression is the emergence of an additional mutation, called a resistant mutation, T790M. Tarceva or Iressa are ineffective against T790M. AstraZeneca found the way to overcome this resistance by inventing Osimertinib (Tagrisso). It turned out to be such a great drug that oncologists started using it as a first line treatment instead of chemotherapy, Iressa or Tarceva. Osimertinib is less toxic and more effective. And as David Epstein mentioned, patients treated with Osimertinib never develop T790M mutation. However, after some years on Osimertinib, patients become resistant to this drug as well. Why? Because new mutations emerge. Some of them are in EGFR again, some are in other proteins. Most common mutation in EGFR causing resistance to Osmertinib, is C797S. In addition, several less common Osimertinib resistance mutations were identified. To make EGFR mutation landscape more complicated, these Osimertinib resistance mutations can co-exist with other so-called intrinsic mutations. Now, how BDTX-1535 can help? It can block activation of EGFR caused by Osimertinib-resistant mutations and EGFR intrinsic mutations. Possibly it doesn’t work so good against T780M, but after Osimertinib you don’t have it. In GBM, EGFR mutations are different and one of the reasons why Osimertinib doesn’t work in GBM could be low brain penetrance.

Interesting publication:

https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-022-00372-6

Point taken.

I think what i was trying to get at was whether BDTX-1535 will demonstrate any effectiveness against
exon 20 insertion or T790M mutations.

If i'm reading the clinical site and BDTX presentation correctly exon 20 and T790M are omitted from the NSCLC trial, however are not omitted from the GBM part.

Osimertinib appears to be ineffective on both mutations which are known to be resistant to TKIs.

https://pubmed.ncbi.nlm.nih.gov/36994936/

Other refs:

https://classic.clinicaltrials.gov/ct2/show/NCT05256290

https://investors.blackdiamondtherapeutics.com/static-files/e5782d24-154c-4d23-af99-a5c3b3b3f9e1

Quote from another board. ($BDTX 5.10 gapping up, daily chart looks sweet)

BDTX-1535 profile already separates it from other agents in EGFRmut NSCLC.

BDTX: Must read BDTX presentation

...for serious BDTX investors

https://investors.blackdiamondtherapeutics.com/static-files/e5782d24-154c-4d23-af99-a5c3b3b3f9e1

(Thanks for the clarification on Biotech Growth - Curacao looks like a more interesting destination to visit though)
https://www.curacao.com/en/

Interesting examples.

Interesting story behind Sunvozertinib:

https://www.evaluate.com/vantage/articles/events/conferences/asco-2023-dizal-heralds-super-tagrisso

Mobocertinib was also recently approved in China based on Phase 1/2 data:

https://www.takeda.com/newsroom/newsreleases/2023/takedas-exkivity-mobocertinib-receives-approval-from-the-nmpa-of-china-becoming-the-first-and-only-therapy-available-for-patients-with-egfr-exon20-insertion-nsclc/

These examples may serve some purpose, however we still need to wait on BDTX for the GBM phase 1 results which imo, go deeper down the mutational progression. This is where there could be some separation in the spectrum of therapy application, imo.

Another 1M shares are purchased by Biotech Growth N V.
https://investors.blackdiamondtherapeutics.com/static-files/825570ab-52f3-4b2a-b862-78d94a857b59
BTW, Biotech Growth NV is a private equity fund managed by BB Biotech which is located in Switzerland.