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This appears to be further Chinese validation of SRA737.....Citizen79 - it would be particularly interesting to hear your thoughts on this.

"Administration of a CHK1 inhibitor prevents the structural remodeling of LINC01956, thereby blocking up-regulation of MGMT and restoring sensitivity to TMZ in vitro and in mouse models of disease, suggesting a potential treatment option to resensitize resistant MGMT promoter–methylated glioblastoma to TMZ."....

..."Using patient-derived xenograft (PDX) and tumor organoid models, we found that treatment with the CHK1 inhibitor SRA737abolishes TMZ-induced structural remodeling of LINC01956 and subsequent MGMT up-regulation, resensitizing TMZ-resistant MGMT promoter–methylated GBM to TMZ. In conclusion, these findings highlight a mechanism underlying temozolomide-induced RNA structural remodeling and may represent a potential therapeutic strategy for patients with TMZ-resistant MGMT promoter–methylated GBM"

https://www.science.org/doi/10.1126/scitranslmed.ado1573

Roche buys Regor’s CDK inhibitors for $850M upfront amid push to develop 20 ‘transformative’ medicines

Ayisha Sharma

News Reporter

Roche is spending $850 million upfront to buy Regor Pharmaceuticals’ suite of next-generation CDK inhibitors as it doubles down on its strategy to prioritize three therapeutic categories, including oncology.

Cambridge, MA-based Regor announced the deal on Monday morning. The company is also eligible for undisclosed milestones, in addition to the upfront payment.

Regor is developing two Phase 1 assets: RGT-419B for breast cancer and RGT-587 for brain metastases. The former is the only CDK4 inhibitor with “single agent efficacy” in refractory ER+/HER2- breast cancer, according to Regor.

The biotech is expected to advance the two candidates through Phase 1 development. After that, Roche’s Genentech is set to take the reins on global clinical development, manufacturing and commercialization activities. The transaction is set to close by the end of the year.

During the company’s pharma day in London on Monday morning, Roche Pharmaceuticals CEO Teresa Graham described the deal as a “perfect fit” with Roche’s breast cancer franchise. The Swiss pharma has three key breast cancer drugs on the market — Perjeta, Kadcyla and Phesgo, which generated CHF 3.7 billion ($4.38 billion) in sales in the first half of the year.

A fourth treatment may be on its way. The FDA is set to decide whether to approve inavolisib for first-line PIK3CA-mutated hormone receptor positive breast cancer by Nov. 27, and an approval in Europe may follow in 2025. Graham said the company expects inavolisib to bring in between CHF 2 billion ($2.37 billion) and CHF 3 billion ($3.55 billion) in peak sales.

Thomas Schinecker

Roche’s oncology pipeline is one of three “shared priority areas” alongside neurology and cardiovascular reno-metabolism, which are expected to account for 80% of Roche’s future growth, Graham said. Roche decided to focus on them in part because they could account for around half of the global disease burden by 2035, CEO Thomas Schinecker said at the event. He also said the company plans to launch 20 “transformative” medicines from 2020 through 2029 for diseases with the “highest societal burden.”

The next three priorities for the company will be infectious disease, immunology and ophthalmology. While ophthalmology has a smaller market potential compared with the others, it will likely become a more significant opportunity as populations age, Graham said.

Vabysmo is currently the “center stone” of that franchise, with approvals in wet age-related macular degeneration, diabetic macular edema and retinal vein occlusion, generating CHF 1.79 billion ($2.12 billion) in half-year sales. The company is also hopeful for a preclinical candidate targeting the Wnt pathway partnered with AntlerA.

Hi Celtic,

No, SRA737 which leverages the concept of synthetic lethality through the inhibition of CHK1, particularly in cancer cells with high replication stress, defective DNA repair mechanisms, or compromised checkpoint controls.

ATB

Interesting observation “nothing in synthetic lethality”…..yet!

https://x.com/paras_biotech/status/1837531057286971791?s=46

The July RNS states:

“ The Company expects that further data, unblinded from drug/placebo recipients, including details of any mild or moderate adverse events and biomarkers of TYK2 and/or JAK1 inhibition, will be available in Q3 2024.”

It doesn’t say that the bod will provide an update based on the further data in Q3.

Obviously the hope is that we get a comprehensive, unambiguous, positive and very carefully worded update next week but it wouldn’t be surprising if we don’t. To coincide with the update whenever it comes, and assuming it is positive, it would be astonishing if the bod don’t capitalise on the opportunity to go to town with a dynamic, energetic and sparkling PR round to mark the culmination of 20 years of incredibly hard and diligent work by Tim and John. One can only hope and pray that the good news of great data isn’t outweighed by the news of how funding, of whatever is required to package the data for a licensing, T/O etc is to be achieved.

GLA

Https://link.springer.com/article/10.1007/s00125-024-06267-5

Good morning SOG,

….which translates to ‘1801/2 are probably better than most current competitors’ … correct?

Https://x.com/natrevrheumatol/status/1833133908252389398?s=46

Https://www.nature.com/articles/s41584-024-01153-1

Potnak - it’s not really what some here think but rather what the bod have either explicitly stated or intimated. No.

Yes Potnak, however the strategy will be dynamic in the face of the prevailing circumstances. If 2 or 3 Pharma are expressing serious interest the bod would have to consider offers in the context of shareholder’s best interests.

Bobbler - £300m - £3 per share most certainly wouldn’t get my vote.

ATB

Hi Potnak, if the data are as good as many expect my guess is they’ll negotiate a very significant buyout. That said Sareum have a habit of coming up with the unexpected so G-d only knows what will happen……all intensely frustrating and exciting at the same time!

“… data from our Phase 1a trial, indicating our inhibitor could confer significant advantages over other TYK2/JAK1 kinase inhibitors.”

Significant advantages over other TYK2/JAK1 kinase inhibitors….bloody wow!!

So 1801 potential best in class in an increasingly validated area and 1802 potential first/best and only TYK2/JAK1 in cancer. Plus Aurora Flt3 and SKIl…. £500m wouldn’t open negotiations!

It’s all hanging in the balance and we’ll know soon but TM/JR and SP haven’t spent 20 years to give it away!!

Good afternoon PCS,

Hopefully by the time you get back from your hols we will have a much clearer sense of where Sareum is heading. I absolute share the frustrations but am entirely confident that SP is working vigorously for the benefit of shareholders!

Have a great break.

Well done Sheephatch….you won’t regret your purchase!

ATB

The FDA is assembling its Oncologic Drugs Advisory Committee next month to discuss whether a biomarker should be used to select patients with certain stomach and esophageal cancers for treatment with checkpoint inhibitors.

Cumulative data suggest the expression of a protein called PD-L1 could be used to predict the benefit of checkpoint inhibitors in some patients with gastric and gastroesophageal junction cancers and esophageal squamous cell carcinoma, the FDA said in an announcement. However, blockbuster drugs such as Merck’s Keytruda and Bristol Myers Squibb’s Opdivo have been approved in broader patient populations, regardless of PD-L1 status.

Regulators also noted that “clinical trials have used different approaches to assess PD-L1 expression and different thresholds to define PD-L1 positivity.”

On Sept. 26, the FDA will ask ODAC to weigh in on the adequacy of PD-L1 as a predictive biomarker and whether the regulators should “restrict the approvals of immune checkpoint inhibitors based on PD-L1 expression.”

The committee will discuss existing approvals for Opdivo, Keytruda and Yervoy, as well as pending applications for BeiGene’s tislelizumab, or Tevimbra.

Ian Waxman, Bristol Myers’ VP and senior global program lead in late-development oncology, said Opdivo regimens have “changed the outlook” for patients with gastric and esophageal cancers, “regardless of PD-L1 status.”

The company stressed that its CheckMate-649 trial, which supported approval for adults with gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma, demonstrated a statistically significant overall survival benefit regardless of patients’ PD-L1 status.

A Merck spokesperson also highlighted Keytruda’s “important role” in advanced gastric and esophageal cancers, adding that it looks forward to a “productive conversation with the FDA’s ODAC.”

BeiGene noted that “the approvability of Tevimbra for the first-line treatment of patients with locally advanced unresectable or metastatic G/GEJ adenocarcinoma and ESCC is not under discussion for this ODAC.”

The company is seeking an all-comer label in both applications.

Https://endpts.com/fda-to-host-adcomm-on-pd-l1-as-a-predictive-biomarker-for-checkpoint-inhibitors/

Good afternoon C79,

Another nice find and good to see still further validation of TYK2!!

As previously stated by TM/JR, the ‘initial’ focus of the 1801 is with psoriasis, which, if I understand correctly is because there are plenty of data from other trials against which 1801 can be compared. Given that there are numerous other conditions in which 1801 may be efficacious it will be interesting to see where we end up. I recall Thoth used to highlight sepsis as a potentially huge market and currently unserved condition but of course there are many others. Not long now until we find out!

“SDC-1801 is a dual TYK2/JAK1 kinase inhibitor being developed as a potential new therapeutic for a range of autoimmune diseases with an initial focus on psoriasis, an autoimmune condition affecting the skin.”

Https://otp.tools.investis.com/generic/regulatory-story.aspx?cid=410&newsid=1855898

Interesting to note the FDA’s award of ‘breakthrough therapy’ status for a Phase 1 cancer target. Given the unique position of SDC 1802 as potentially the only current TYK2 JAK1 in the cancer space, albeit as yet pre-clinical and assuming the 1801 data are as positive as many anticipate, could 1802 be granted breakthrough status in due course?