Memorial Sloan Results Imminent, page-13

This Phase 1 cancer trial completed last year - has just resulted in a June 2022 US$ 1 billion plus  bigPharma deal.

Good story here - note the dates.  Results a bit ho hum - but the small Canadian cancer company still managed this deal.

This recent phase 1 deal is relevant aright, to the worth of paxalisib....post success in these forthcoming results.

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Phase 1 results - more below

The potent and highly selective RP-3500 achieved meaningful clinical benefit across a variety of gene alterations in 34 of 69 evaluable patients (49%), including 12 patients with objective tumor responses, 14 patients with RECIST-defined stable disease for at least 16 weeks, and eight patients with early significant decreases in tumor markers and tumor shrinkage.

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ATR, a sub protein kinase in the PI3K family  -   

I know there is no comparison between these 2 drugs, but hey - they have the deal .....Kazia ???


Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein 1 (FRP1) is an enzyme that, in humans, is encoded by the ATR gene.^[5][6] ATR belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

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Repare stock soars after Montreal cancer drug developer strikes US$1-billion-plus deal with Roche
PUBLISHED JUNE 2, 2022
  
Shares in Montreal cancer drug developer Repare Therapeutics Inc.  soared Thursday after the company announced a deal with pharmaceutical giant F. Hoffmann-La Roche AG that could be worth north of US$1-billion to the Canadian startup.

Repare’s share price increased by more than 40 per cent on the Nasdaq exchange after the company revealed late Wednesday it had entered into a worldwide licence and collaboration agreement with Roche to develop and commercialize the Montreal company’s drug camonsertib, also known as RP-3500.

RP-3500 is the lead molecule of a series of “precision oncology” drugs Repare is developing that attack genetic defects in cancerous tumours, preventing toxic cells from repairing their DNA. The goal is to treat smaller patient groups based on their genetic makeup, with the hope the drugs will respond more effectively while generating fewer side effects.

Repare will receive US$125-million upfront from Roche and up to US$1.2-billion if its drug reaches a series of clinical, regulatory, commercial and sales milestones. Repare also stands to earn royalties on sales if the drug makes it to market.

“Roche is excited about the emerging DNA damage response field, which represents a promising new approach to precision oncology,” James Sabry, global head of pharma partnering with the Swiss giant, said in a release. He called RP-3500 “a new potential treatment option for patients with significant unmet needs across a range of tumor types.”

The deal is a bright spot for a biotechnology sector that has suffered severe stock price devaluation in the past few quarters in Canada and elsewhere, mirroring the broad selloff of technology stocks in the face of rising interest rates and inflation and economic uncertainty. With Thursday’s gains, Repare shares are still trading at about a third of their 52-week high price of US$35.75. It closed Thursday at US$12.67, up 44.8 per cent.

Bloom Burton analyst David Martin nicknamed RP-3500 “the Rodney Dangerfield of oncology drugs” in an April research report, arguing that, like the late comic, the drug “got no respect” despite promising early clinical data from human trials on the drug published in the past year.

In the face of investor indifference to a potential “blockbuster drug,” Mr. Martin said in an interview that “a licensing deal like this is a very nice monetizing event, especially given the company’s pipeline behind RP-3500″ and the company’s drug discovery technology. He added it was one of the larger product licensing deals across the sector in the past two years and one of the largest ever in Canada.
Repare chief executive officer Lloyd Segal said in an interview the Roche partnership marked an important moment for the company, providing validation and a deep-pocketed partner that could shepherd the drug through large-scale trials during what could be a prolonged period of bleak capital markets activity.


ATR inhibitor RP-3500 demonstrates safety and early clinical benefit


Early data from a biomarker-driven Phase I trial of ATR inhibitor RP-3500 shows encouraging results for patients with advanced solid tumors harboring selected molecular alterations

MD Anderson News Release October 08, 2021

In a first-in-human, Phase I trial, researchers at The University of Texas MD Anderson Cancer Center discovered that ATR inhibitor RP-3500 was safe and well tolerated with promising clinical benefit. Principal investigator Timothy A. Yap, Ph.D., associate professor of Investigational Cancer Therapeutics, today presented initial data from the trial at the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics.

The trial is the largest biomarker-selected study to test an ATR inhibitor as a single agent in cancers harboring synthetic lethal genomic alterations in DNA damage repair (DDR) pathways. Yap and his team observed preliminary antitumor efficacy in patients with advanced solid tumors — including ovarian, prostate and breast cancers — that were resistant, refractory or intolerant to standard therapy, including BRCA1 and BRCA2 mutated cancer patients who had previously received PARP inhibitor treatment. The potent and highly selective RP-3500 achieved meaningful clinical benefit across a variety of gene alterations in 34 of 69 evaluable patients (49%), including 12 patients with objective tumor responses, 14 patients with RECIST-defined stable disease for at least 16 weeks, and eight patients with early significant decreases in tumor markers and tumor shrinkage.

“Not only did RP-3500 demonstrate a favorable and differentiated safety profile, but our initial data also showed promising and distinct early efficacy,” Yap said. “Although this Phase I study has only had approximately nine months of dosing at efficacious doses of 100mg or more of RP-3500, we are encouraged by what we have observed so far in this hard-to-treat advanced cancer patient population.”

Various conditions of DNA damage, specifically breaks in the DNA double strand and replication stress, activate a complex network of DDR mechanisms. One of the key mediators of the DDR signaling pathway is the protein kinase ATR, which is activated in response to DNA replication stress — making it a promising therapeutic target in cancers with a range of DDR defects.
Based on a genome-wide CRISPR-based screening platform, 17 biomarkers for sensitivity to RP-3500 — including ATM, BRCA1/2 and other alterations — were identified for prospective patient selection for this trial.

“We were keen to give every patient the best chance of responding by only enrolling those who had at least one of these pre-identified actionable predictive biomarkers of response to RP-3500,” Yap said.

The study enrolled a total of 101 patients with heavily pre-treated advanced solid tumors carrying synthetic lethal genomic alterations that researchers predicted for ATR inhibitor sensitivity. The primary endpoints of the study were safety and tolerability, as well as recommended phase 2 dose (RP2D) and optimal schedule. Other endpoints included pharmacokinetics, pharmacodynamics and preliminary antitumor activity.

Patients were treated on different doses and schedules of RP-3500. Treatment emergent adverse events of all grades most commonly included grade 1-2 anemia, fatigue and decreased appetite. Grade 3 anemia was observed in 21.8% of all patients treated. No grade 4 or worse anemia was reported during the trial.

After assessing the adverse events, pharmacokinetic, pharmacodynamic and antitumor activity, the researchers determined the RP2D of RP-3500 to be 160mg once daily for three days, followed by four days off.
Early analysis of antitumor activity shows promising clinical activity across a spectrum of tumor types and genetic alterations, including ATM or CDK12-mutated castration-resistant prostate cancer, PARP inhibitor-resistant ovarian cancer with BRCA1 or RAD51C mutations, BRCA1-mutated ER+ breast cancer, BRCA1 mutated head and neck squamous cell carcinomas and BRCA2 mutated melanoma.

While the study is ongoing, Yap is encouraged by the initial data and will soon open enrollment to the TRESR Phase II expansion cohorts.

“Our promising early clinical data of this potent and highly selective ATR inhibitor offer a clear direction for further development of RP-3500,” Yap said. “We will continue to assess RP-3500 in patients with defined molecular alterations and also in novel rational combinations.”