On December 2, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported key clinical updates from its RAS(ON) inhibitor portfolio. The data to be presented during an investor webcast today at 8:00 a.m. Eastern Time (ET) will focus on updated clinical data from the Phase 1 RMC-6236 monotherapy study in pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) (Press release, Revolution Medicines, DEC 2, 2024, View Source [SID1234648725]). In addition, new clinical data will be provided from several combination studies, including those evaluating RMC-6236 with pembrolizumab, RMC-6291 with pembrolizumab, and the first-of-its-kind RAS(ON) inhibitor doublet combination of RMC-6291 and RMC-6236.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our mission is to revolutionize treatment for patients with RAS-addicted cancers, and our ongoing progress is supported by the clinical milestones we continue to achieve in patients with a range of RAS mutant tumor types, stages of disease and lines of therapy," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "We’ve now reported initial clinical validation of three differentiated RAS(ON) inhibitors, shown evidence of promising initial clinical activity and tolerability profiles in patients with three common, difficult-to-treat RAS-addicted tumors, and shared growing evidence of clinical impact delivered through three potential treatment paradigms – as monotherapy, in combination with pembrolizumab, and as RAS(ON) inhibitor doublets. With these compelling results, we are in a strong position to pursue an expansive set of late-stage development opportunities on behalf of patients with RAS-addicted cancers, beginning with the ongoing and pending pivotal trials."

RMC-6236 Monotherapy Study
RMC-6236-001 is a multicenter, Phase 1/1b study designed to evaluate RMC-6236, a RAS(ON) multi-selective inhibitor, as monotherapy, in patients with advanced solid tumors. As of September 30, 2024, a total of 436 patients were treated across NSCLC (n=132) and PDAC and other solid tumors (n=304) cohorts. Patients were treated across a range of doses, from 10 mg to 400 mg once daily (QD).

PDAC Cohort
As an update to data reported at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) conference in October 2024, the company shared a new analysis of safety and activity data from the July 23, 2024 data cutoff date in patients with previously treated PDAC treated with a 300 mg QD dose, the same dose used in the ongoing RASolute 302 Phase 3 PDAC trial.

Key findings:

In 76 patients with RAS mutant PDAC, RMC-6236 at 300 mg QD was generally well tolerated and showed an overall safety profile consistent with the results reported at ENA. No differentiated safety signals were observed.

The most common treatment-related adverse events (TRAEs) were rash and gastrointestinal (GI)-related toxicities that were primarily Grade 1 or 2 in severity. No Grade 3 or higher TRAEs were observed in greater than 10% of patients.

There were no treatment discontinuations due to TRAEs and the mean dose intensity was 89%.

In 37 patients with 2L RAS mutant PDAC, RMC-6236 at 300 mg QD demonstrated compelling antitumor activity.

Patients with PDAC harboring a KRAS G12X mutation (n=22) achieved a median PFS of 8.8 months (95% confidence interval (CI), 8.5 months – not estimable (NE)), while the median OS was not estimable (95% CI, NE – NE). Patients with PDAC harboring any RAS mutation (n=37) achieved a median PFS of 8.5 months (95% CI, 5.9 months – NE), while the median OS was not estimable (95% CI, 8.5 months – NE).

The proportion of patients who remained alive six months after starting treatment with RMC-6236 was 100% and 97% in patients with PDAC harboring a KRAS G12X mutation and patients with PDAC harboring any RAS mutation, respectively.

The objective response rate (ORR) was 36% and 27% in patients with PDAC harboring a KRAS G12X mutation and patients with PDAC harboring any RAS mutation, respectively.

RASolute 302, the company’s randomized Phase 3 study of RMC-6236 versus standard of care chemotherapy in 2L patients with previously treated metastatic PDAC, is currently ongoing.

Next steps:

Based on the encouraging monotherapy data update, the company aims to advance RMC-6236 into earlier lines of therapy for patients with metastatic PDAC.

NSCLC Cohort
As an update from a smaller initial cohort reported at ESMO (Free ESMO Whitepaper) 2023, data from a September 30, 2024 data cutoff date were reported for 124 patients with previously treated RAS mutant NSCLC who received RMC-6236 at clinically active doses in the range of 120 mg to 300 mg QD.

Key findings:

In patients with previously treated NSCLC, RMC-6236 was generally well tolerated at doses of 120 mg to 220 mg QD, while the 300 mg QD dose demonstrated a higher frequency and severity of TRAEs.

In the 120 mg to 220 mg dose range, the most common TRAEs were rash and GI-related toxicities that were primarily Grade 1 or 2 in severity. No Grade 3 or higher TRAEs were observed in greater than 10% of these patients. In the 120 mg to 220 mg dose range, TRAEs leading to dose modification occurred in 41% of patients with 4% of patients discontinuing treatment due to TRAEs and the mean dose intensity was 88%.

RMC-6236 at 120 mg to 220 mg QD demonstrated encouraging antitumor activity in the population of 40 efficacy-evaluable 2L or third-line (3L) patients with NSCLC who had received immunotherapy and platinum chemotherapy but had not received docetaxel.

These patients achieved a median PFS of 9.8 months (95% CI, 6 – 12.3 months), a median OS of 17.7 months (95% CI, 13.7 months – NE) and an ORR of 38%.

Next steps:

The company expects to initiate RASolve 301, a randomized Phase 3 study of RMC-6236 versus docetaxel in patients with previously treated, locally advanced or metastatic RAS mutant NSCLC, in the first quarter of 2025.

RAS(ON) Inhibitor Combination Studies

RMC-6236 with Pembrolizumab
RMC-LUNG-101B is an arm of the Phase 1b study of RMC-6236 in combination with pembrolizumab, with or without chemotherapy, in patients with RAS mutant NSCLC. A total of 20 patients treated with RMC-6236 at 200 mg QD and pembrolizumab at the standard dose of 200 mg once every three weeks (Q3W) were evaluated as of an October 28, 2024 data cutoff date. The median duration of treatment for these patients was 2.3 months.

The combination of RMC-6236 with pembrolizumab was generally well tolerated and the safety profile was consistent with previously reported results for the individual agents. TRAEs of Grade 1 aspartate aminotransferase (AST) elevation were reported in two patients (10%) and a TRAE of Grade 2 AST elevation was reported in one patient (5%). A TRAE of Grade 1 alanine transaminase (ALT) elevation was reported in one patient (5%) and a TRAE of Grade 3 ALT elevation was reported in one patient (5%). The mean dose intensity for RMC-6236 was 97%.

Next steps:

The company believes the data from this study support continued evaluation of the combination of RMC-6236 with pembrolizumab in 1L NSCLC patients.

RMC-6291 and RMC-6236 RAS(ON) Inhibitor Doublet
RMC-6291-101 is a Phase 1b study of RMC-6291 in combination RMC-6236 in patients with RAS G12C mutant solid tumors. The study has evaluated RMC-6291 at doses of 100 mg or 200 mg BID and RMC-6236 at a dose range of 100 mg to 300 mg QD. As of an October 28, 2024 data cutoff date, 74 patients were evaluated for safety with a median duration of treatment of 2.3 months.

The combination of RMC-6291 with RMC-6236 was generally well tolerated across all dose levels evaluated. The most common TRAEs were rash and GI-related toxicities that were primarily Grade 1 or 2 in severity. No Grade 3 or higher TRAEs were observed in greater than 5% of patients. One Grade 4 TRAE of hypokalemia was associated with Grade 3 diarrhea. TRAEs leading to dose interruption or reduction occurred in 30% and 10% of patients, respectively. The mean dose intensities for RMC-6291 and RMC-6236 were 95% and 92%, respectively.

A subset of efficacy-evaluable patients with colorectal cancer (CRC) who were previously treated with a KRAS(OFF) G12C inhibitor was evaluated for antitumor activity on treatment with RMC-6291 with RMC-6236. As reference values, the company also reported that the ORR for patients with CRC treated with RMC-6236 monotherapy at a dose of 300 mg daily in the RMC-6236-001 study as of a data cutoff date of September 30, 2024 was 9%, and the ORR for patients with CRC previously treated with a KRAS(OFF) G12C inhibitor who were subsequently treated with RMC-6291 monotherapy at a dose of 200 mg twice daily in the RMC-6291-001 study as of a data cutoff date of October 28, 2024 was 0%. In the combination study, patients with CRC who were previously treated with a KRAS(OFF) G12C inhibitor and who received their first doses of the two study drugs at least 8 weeks prior to data cutoff were included in the analyses (n=12). The ORR was 25%, including one patient with an unconfirmed complete response, and the DCR was 92%. The median treatment duration was 2.3 months.

Next steps:

The company believes the data from this combination study support continued development of RAS(ON) doublets in a broad range of tumor types and earlier lines of therapy.

RMC-6291 with Pembrolizumab
RMC-LUNG-101A is an arm of the Phase 1b study of RMC-6291, a RAS(ON) G12C-selective inhibitor, in combination with pembrolizumab, with or without chemotherapy, in patients with RAS G12C mutant NSCLC. A total of 15 patients treated with RMC-6291 at 200 mg twice daily (BID) and pembrolizumab at the standard dose of 200 mg Q3W were evaluated as of an October 28, 2024 data cutoff date. As of this date, 47% of these patients had been on treatment for 60 days or more.

The combination of RMC-6291 with pembrolizumab was generally well tolerated and the safety profile was consistent with previously reported results for the individual agents. A TRAE of Grade 1 AST elevation was reported in one patient (7%) and a TRAE of Grade 1 ALT elevation was reported in one patient (7%). There were no TRAEs of Grade 2 or higher AST or ALT elevations reported. The mean dose intensity for RMC-6291 was 98%.

Next steps:

The company believes the three pairwise combinations of RMC-6291 with RMC-6236, RMC-6236 with pembrolizumab and RMC-6291 with pembrolizumab justify investigation of the triplet combination of RMC-6291 and RMC-6236 with pembrolizumab as a potential chemotherapy-sparing option for patients with 1L NSCLC.

Investor Webcast
The Revolution Medicines investor webcast will begin at 8:00 a.m. Eastern Time. A link to participate in the live webcast can be accessed here and is also available on the Events and Presentations section of Revolution Medicines’ investor website at View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

On December 2, 2024 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, reported that it has commenced an underwritten public offering to sell up to $600.0 million of shares of its common stock (Press release, Revolution Medicines, DEC 2, 2024, View Source [SID1234648724]). All of the shares of common stock are being offered by Revolution Medicines. In addition, Revolution Medicines intends to grant the underwriters a 30-day option to purchase up to an additional $90.0 million of shares of common stock. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

J.P. Morgan, TD Cowen, Goldman Sachs & Co. LLC and Guggenheim Securities are acting as joint book-running managers for the proposed offering. UBS Investment Bank is acting as lead manager.

A shelf registration statement relating to these securities was filed with the U.S. Securities and Exchange Commission (SEC) on March 4, 2024, and automatically became effective upon filing. This offering is being made solely by means of a prospectus. A copy of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained for free by visiting EDGAR on the SEC’s website at www.sec.gov. Alternatively, a copy of the preliminary prospectus supplement and the accompanying prospectus relating to this offering may be obtained by contacting: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by email at [email protected] and [email protected]; TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by telephone at (855) 495-9846 or by email at [email protected]; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526 or by email at [email protected]; and Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, New York 10017, by telephone at (212) 518-9544 or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 2, 2024 Rakovina Therapeutics Inc. (TSX-V: RKV, the "Company"), a biopharmaceutical company committed to advancing new cancer therapies based on novel DNA-damage response technologies, reported the financial results for the third quarter ending September 30, 2024, and provides an update to corporate activities (Press release, Rakovina Therapeutics, DEC 2, 2024, View Source;utm_medium=rss&utm_campaign=rakovina-therapeutics-announces-2024-q3-financial-results-and-provides-corporate-update [SID1234648723]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"I couldn’t be more proud of the Rakovina Therapeutics team and the remarkable progress we’ve made together in 2024," said Executive Chairman Jeffrey Bacha. "Artificial intelligence is no longer just the future of drug development—it’s the reality we’re building today. We are privileged to have world-class experts driving the integration of cutting-edge AI with our laboratory infrastructure at the University of British Columbia. What we’ve accomplished so far is just the beginning—a glimpse of what’s possible as we advance our innovative cancer therapy platform.

The overwhelming support from our investors, exemplified by the upsized investment offering announced this week, is both humbling and deeply motivating. These additional funds will play a critical role in unlocking the transformative opportunities that await us in 2025 as we continue our mission to develop life-changing treatments for cancer patients," he added.

2024 Q3 Highlights and Recent Developments: Rakovina continues to hit 2024 milestones

On September 17, 2024, we broadened our capabilities in AI through a collaboration with Variational AI. This partnership grants Rakovina exclusive rights to compounds generated by Variational’s Enki platform, specifically tailored to selected target product profiles, along with an option to license validated drug candidates for further development. The Enki platform will provide novel inhibitors of specific DDR kinase targets identified by Rakovina Therapeutics. Our team will synthesize and assess the potential of these candidates as cancer therapies at our state-of-the-art laboratories at the University of British Columbia. By combining Variational AI’s expertise in kinase drug discovery with our focus on DDR pathways, we aim to enhance partnering opportunities, particularly as "big pharma" continues to prioritize innovative therapies targeting these critical pathways.
On October 23, 2024, we announced receipt of the initial results from the proprietary Deep Docking AI platform. The Deep Docking algorithm was able to evaluate billions of molecular structures to develop a short-list of drug candidates that have been optimized to a specific target-product profile. With the AI platform, results were achieved in less than five months—a feat not capable through traditional methods of discovery. The selected drug candidates will be synthesized for validation in Rakovina Therapeutics’ laboratories at the University of British Columbia during the coming months with the goal of advancing a best-in-class DDR drug candidate to human clinical trials in collaboration with pharmaceutical company partners.
In October and November 2024, we had the privilege of presenting our latest research from our PARP1/2 inhibitor KT-3000 program and our AI-driven drug discovery initiatives at two prestigious conferences. At the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in Spain, we highlighted innovative findings from the KT-3000 series, a promising class of PARP1/2 inhibitors. And at the 29th Annual Meeting of the Society for Neuro-Oncology (SNO), we presented compelling data on a shortlist of targeted therapies identified through our Deep Docking AI platform. Notably, early studies suggest that these PARP inhibitor compounds have the potential to cross the blood-brain barrier—an achievement that positions them as significant candidates for advancing treatments in areas of critical unmet need, including neurological cancers.
On November 27, 2024, we announced a non-brokered private placement financing of units priced at $0.06 per unit, with each unit consisting of one common share and one common share purchase warrant with an exercise price of $0.10 per warrant and a term of two years, for gross proceeds to the Company of $1.25 Million (the "Offering").
On November 28, 2024, we announced that due to high investor demand, the Offering would be increased to $2.5 Million (subject to exchange approval).
Summary of Financial Results for the quarter ended September 30, 2024

For the three and nine months ended September 30, 2024, the Company reported a net loss of $1,015,667 and $2,588,630, respectively. Research and development expenses were $678,299 and $1,597,067 for the three and nine months ended September 30, 2024, respectively. General and administrative expenses were $268,909 and $796,183 for the three and nine months ended September 30, 2024, respectively. Total cash expenses related to research and development and general and administrative expenses for the three and nine months ended September 30, 2024, were $793,867 and $1,922,037, respectively.

Selected Financial Information

As at September 30, 2024
Cash & cash equivalents $255,049
Working capital $358,060
Intangible assets $4,112,602
Total Assets $5,308,181
Total liabilities $2,233,687
Deficit $(13,513,941)
Total equity $3,074,494
Statements of net loss and comprehensive loss data:

For the nine months ended September 30, 2024 For the nine months ended September 30, 2023
Research & Development $1,597,067 $1,252,165
General and Administrative $796,183 $568,496
Net loss and comprehensive loss $2,588,630 $1,890,162
Basic and diluted income (loss) per share $(0.03) $(0.03)
Operating cash burn $1,922,037 $1,328,271
Weighted average shares outstanding 76,660,137 69,829,500
Rakovina Therapeutics’ financial statements as filed with SEDAR+ can be accessed from the Company’s website at: View Source

Senior management of Rakovina Therapeutics will hold an information and update webinar on December 4, 2024, at 3 PM Pacific Time/6 PM Eastern Time. Interested parties may sign up at https://bit.ly/rakovina-q3.

On December 2, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, reported positive final results from the randomized Phase 2 study of its lead oncology drug, CM24, a humanized monoclonal antibody that blocks CEACAM1, in patients with pancreatic ductal adenocarcinoma (PDAC) (Press release, Purple Biotech, DEC 2, 2024, View Source [SID1234648722]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very excited about the final data, demonstrating CM24’s clear and consistent improvement across all efficacy endpoints evaluated in our randomized Phase 2 study," stated Purple Biotech CEO Gil Efron. "The enhanced results in patients with CEACAM1 and other serum markers gives us further optimism that a biomarker enriched patient population selection could further strengthen CM24’s magnitude of efficacy, potentially positioning CM24 as a treatment for multiple CEACAM1-expressing malignancies in line with its mechanism of action."

Michael Cecchini, MD Associate Professor of Medicine at the Yale Cancer Center, a principal investigator in this study, commented, "The promising results in PDAC, along with the identification of a potential patient subgroup that may benefit from targeting CEACAM1 and NET serum levels, potentially position CM24 as an encouraging treatment option. As a clinician, it is inspiring to see data that suggest the potential for improved outcomes in patients with late-stage metastatic PDAC, who desperately need new and effective therapies. These findings support further investigation of CM24 in combination with a checkpoint inhibitor and standard-of-care chemotherapy to improve outcomes not only in PDAC but also in other challenging cancer types."

Summary of Data and Findings:

The Phase 2 study evaluated CM24, a novel first-in-class multi-functional anti-CEACAM1 antibody, in combination with Bristol Myers Squibb’s immune checkpoint inhibitor nivolumab plus stand-of-care (SoC) chemotherapy in second-line metastatic PDAC patients versus SoC chemotherapy alone. CM24 is a humanized monoclonal antibody that blocks CEACAM1, a multi-faceted membrane glycoprotein that is one of the main proteins present on NETs, also acting as a pro-angiogenic and anti-apoptotic agent collectively promoting tumor invasiveness, metastasis and immune evasion.

The primary endpoint of the study is OS and the secondary endpoints include PFS, ORR and disease control rate (DCR). A Bayesian methodology was used to estimate the magnitude of effect of the experimental arm versus the SoC arm in each chemotherapy cohort; the study was not powered for hypothesis testing. A total of 63 patients were enrolled, across 18 centers in the U.S., Spain, and Israel in 2 parallel and independent randomized study cohorts (total of 2 arms per cohort). The experimental arms administered patients with CM24 plus nivolumab and a choice of one of two SoC chemotherapies for second-line PDAC, dependent on prior first line therapy regimen; either gemcitabine/nab-paclitaxel or liposomal irinotecan (Nal-IRI)/5-fluorouracil (5-FU) and leucovorin (LV) (Nal-IRI/5FU/LV), while the control arms administered either respective chemotherapy alone. CA19-9 as well as additional exploratory biomarkers were also evaluated. Of the 63 patients enrolled, 32 were in the gemcitabine/nab-paclitaxel study (experimental and control) and 31 were in the Nal-IRI/5FU/LV study (experimental and control). The gemcitabine/nab-paclitaxel-based part of the study was impacted by informative censoring of the control arm that led to an imbalance between the control and experimental arms, rendering this part of the study unsuitable for analysis; this part of the study has no impact on the CM24+nivolumab+Nal-IRI/5FU/LV portion of the study.

The study’s final efficacy results in the Nal-IRI/5FU/LV intent to treat (ITT) cohort population are summarized in the following table:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 16) Nal/IRI/5FU/LV Arm
(n = 15)
Hazard ratio for OS 0.81 (95% CI: 0.38-1.71)
Median OS 7.92 months 5.55 months
6 months OS rate 53 % 47 %

Hazard Ratio for PFS 0.75 (95% CI: 0.35-1.61)
Median PFS 3.9 months 2.0 months
3 months PFS rate 67 % 47 %
6 months PFS rate 17 % 13 %
ORR 25 % 7 %
DCR 63 % 47 %

A consistent and continuous decrease of CA19-9, a clinically validated PDAC biomarker, was observed in the experimental arm reaching a median percentage reduction from baseline of approximately 80% vs. an increase of 40% in the control arm.

Subgroup analysis of patients with a range of pretreatment serum CEACAM1 between 6,000 pg/mL and 15,000 pg/mL, resulted in statistically significant results as follows:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 4)
Nal/IRI/5FU/LV Arm
(n = 7)

Hazard ratio for OS 0.21 (95% CI: 0.04-1.06)
Median OS 9 months 3.9 months
Hazard ratio for PFS <0.1 (95% CI: 0-inf)
Median PFS 4.7 months 1.8 months
ORR 50 % 0 %
DCR 100 % 43 %

An additional subgroup analysis of patients, which comprised 80% of the patients in the study cohort, with a range of pretreatment serum CEACAM1 between 6,000 pg/mL and 15,000 pg/mL together with patients with pretreatment serum Myeloperoxidase (MPO) levels of 200 ng/mL and 600 ng/mL, resulted in statistically significant results as follows:

Metric CM24 + Nivolumab +
Nal/IRI/5FU/LV Arm
(n = 13) Nal/IRI/5FU/LV Arm
(n = 11)
Hazard ratio for OS 0.39 (95% CI: 0.16-0.98)
Median OS 7.90 months 5.50 months
Hazard ratio for PFS 0.28 (95% CI: 0.11-0.73)
Median PFS 4.1 months 1.9 months
ORR 31 % 0 %
DCR 69 % 36 %

Additional biomarkers analysis based on the patient pretreatment biopsies, demonstrated significant OS and PFS benefit (HR 0.1, P=0.013 and HR 0.19, P=0.033, respectively) in patients with both high tumor CEACAM1 (≥100) and low Combined Positive Score (CPS) (≤1) (a measure of PD-L1 positive tumor cells) supporting the CM24/nivolumab combined treatment and its mechanistic rationale, and may open a new opportunity for patients who are not eligible for anti-PD1 therapy in various indications

The CM24+nivolumab+Nal/IRI/5FU/LV regimen was well tolerated, with the most frequent treatment emergent Grade 3 or higher adverse events being diarrhea (4 patients in the experimental arm vs. 1 patient in the control arm), fatigue (2 patients in the experimental arm vs. no patients in the control) and neutropenia (2 patients in the experimental arm vs. no patients in the control). Accordingly, no meaningful difference in safety and tolerability were observed between the experimental arm and SoC arm.

"The significant results in the subgroup based on certain range of serum CEACAM1 and MPO levels, that covered 80% of the patients in the Nal-IRI cohort, is encouraging. We believe that tumors with low CEACAM1 or NETs are less reliant on these targets whereas extremely high levels may suggest potential resistance to the treatment. Based on the emerging role of neutrophil extracellular traps (NETs) in cancer and the positive findings of our study in this selected population overlapping with CEACAM1 expression, we are planning a 3-arm Phase 2b study comparing either CM24 plus a PD1 inhibitor or CM24 monotherapy to SoC in multiple tumor types selected based on their NET and CEACAM1 expressions. This design will also investigate the contribution of parts in regard to the need for PD1 blockade on top of CM24. We plan to target patients with higher serum levels of CEACAM1 and MPO, as they are potentially more likely to benefit from CM24 treatment," stated Dr Michael Schickler, Head of Clinical and Regulatory Affairs.

On December 2, 2024 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology", Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies for breast cancer and beyond, reported a new clinical trial collaboration and supply agreement with Novartis in frontline metastatic breast cancer (Press release, Olema Oncology, DEC 2, 2024, View Source [SID1234648721]). Olema has also entered into a securities purchase agreement for the private placement of approximately $250.0 million of common stock and pre-funded warrants to purchase common stock with new and existing institutional and accredited investors (the "Private Placement").

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are now fully enabled to initiate our planned pivotal Phase 3 clinical trial, OPERA-02, for palazestrant in combination with ribociclib in frontline ER+/HER2- metastatic breast cancer. Our new agreement with Novartis, which includes sufficient ribociclib drug supply for the planned approximately 1,000 patient trial, is a major milestone. When combined with our Private Placement of $250.0 million of common stock and pre-funded warrants with high-quality, long-term investors, Olema now expects to have the necessary resources to execute OPERA-02, the Phase 1/2 study of OP-3136, and the ongoing Phase 3 OPERA-01 monotherapy trial," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "We remain on track to share topline data from OPERA-01 in 2026 and we are excited to present our latest data from the ongoing Phase 1b/2 study of palazestrant in combination with ribociclib at the San Antonio Breast Cancer Symposium (SABCS) next week."

New Clinical Trial Collaboration and Supply Agreement Enables Phase 3 OPERA-02 Trial

Under the terms of the agreement, Novartis will provide Olema with ribociclib drug supply for the planned, Olema-sponsored, Phase 3 OPERA-02 trial of palazestrant in combination with ribociclib in ER+/HER2- frontline advanced or metastatic breast cancer. All clinical data and inventions from the trial will be jointly owned while Olema maintains global commercial and marketing rights to palazestrant.

Private Placement Funds Expanded Clinical Development Activities

The Private Placement is expected to close on or about December 4, 2024, subject to the satisfaction of customary closing conditions. The financing included participation by new and existing investors Adage Capital Partners LP, Bain Capital Life Sciences, BVF Partners L.P., Driehaus Capital Management, Janus Henderson Investors, Paradigm BioCapital Advisors, Wellington Management, Woodline Partners LP, and a large investment manager. Pursuant to the terms of the securities purchase agreement, Olema will issue 19,928,875 shares of common stock at a purchase price of $9.08 per share and pre-funded warrants to purchase up to an aggregate of 7,604,163 shares of common stock at a purchase price of $9.0799 per pre-funded warrant, for gross proceeds of approximately $250.0 million, before deducting placement agent fees and other offering expenses. The pre-funded warrants will have an exercise price of $0.0001 per share of common stock, be immediately exercisable and remain exercisable until exercised in full. The Private Placement is being conducted in accordance with applicable Nasdaq rules and was priced using the average Nasdaq official closing price of Olema’s common stock for the five trading days ended November 27, 2024.

Jefferies is acting as lead placement agent with J.P. Morgan, Citigroup, Goldman Sachs & Co. LLC, LifeSci Capital, Oppenheimer & Co., and H.C. Wainwright & Co. acting as placement agents in the Private Placement.

Olema intends to use the net proceeds from the Private Placement, together with its current cash, cash equivalents and marketable securities, to fund the OPERA-02 trial, the Phase 1/2 study of OP-3136, and its ongoing Phase 3 OPERA-01 monotherapy trial of palazestrant, and for working capital and general corporate purposes.

The securities described above have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state’s securities laws, and are being issued and sold pursuant to an exemption from registration provided for under the Securities Act. Accordingly, these securities may not be offered or sold in the United States, except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act. Olema has agreed to file a registration statement with the U.S. Securities and Exchange Commission (the "SEC") registering the resale of the shares of common stock issued and sold in the Private Placement. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

About Palazestrant (OP-1250)

Palazestrant (OP-1250) is a novel, orally available small molecule with dual activity as both a complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In preclinical studies, palazestrant completely blocks ER-driven transcriptional activity in both ESR1 wild-type and mutant forms of breast cancer. In Olema’s ongoing clinical trials for advanced or metastatic ER+/HER2- breast cancer, palazestrant has demonstrated anti-tumor activity along with attractive pharmacokinetics and exposure, favorable tolerability, and combinability with CDK4/6 inhibitors. Palazestrant has been granted U.S. Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. It is being evaluated both as a single agent in an ongoing Phase 3 clinical trial, OPERA-01, and in Phase 1/2 combination studies with CDK4/6 inhibitors (palbociclib and ribociclib), a PI3Ka inhibitor (alpelisib), and an mTOR inhibitor (everolimus).