On November 6, 2023 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported that Dean Schorno, the company’s chief financial officer, will present a company overview at the Jefferies 2023 London Healthcare Conference on Tuesday, November 14, 2023 at 3:30 p.m. GMT (10:30 a.m. EST) (Press release, Rigel, NOV 6, 2023, View Source [SID1234637047]).

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To access the live webcast or archived recording, visit the Investor Relations section of the company’s website at www.rigel.com. Please connect to Rigel’s website prior to the start of the live webcast to allow for any software downloads.

On November 6, 2023 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported its financial results for the quarter ended September 30, 2023, and provided an update on corporate progress (Press release, Revolution Medicines, NOV 6, 2023, View Source [SID1234637046]).

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Recent Highlights

RMC-6236: Revolution Medicines presented promising anti-tumor activity data for RMC-6236, a RASMULTI(ON) Inhibitor, in patients with non-small cell lung cancer (NSCLC) or pancreatic ductal adenocarcinoma (PDAC) harboring KRASG12X mutations. The data demonstrated that treatment with RMC-6236 led to meaningful clinical responses at dose levels that were generally well tolerated. The results also provided clinical validation that RMC-6236 as a RASMULTI(ON) Inhibitor can drive objective responses in patients with tumors carrying multiple common KRAS mutations, including G12D, G12V and G12R. These data support the company’s decision to advance RMC-6236 into late-stage clinical development.

RMC-6291: The company presented encouraging anti-tumor activity data for its mutant-selective RASG12C(ON) Inhibitor, RMC-6291, in patients with advanced solid tumors harboring KRASG12C mutations, including NSCLC and colorectal cancer (CRC). The data provided preliminary evidence of anti-tumor activity by treatment with RMC-6291 that was generally well tolerated across dose levels and included preliminary evidence of mechanistic and clinical differentiation from KRASG12C(OFF) inhibitors as indicated by clinical responses in NSCLC patients previously treated with a KRASG12C(OFF) inhibitor and in KRASG12C(OFF) inhibitor naïve CRC patients.

EQRx Acquisition: Last week, Revolution Medicines announced that Institutional Shareholder Services Inc. and Glass Lewis & Co. recommended Revolution Medicines stockholders vote "FOR" the issuance of Revolution Medicines shares in the previously announced all-stock acquisition of EQRx, Inc. at the special meeting of stockholders scheduled for 11:00 a.m. Eastern Time on November 8, 2023. The transaction is expected to close shortly following the stockholder vote, subject to satisfaction of customary closing conditions, including approval by both Revolution Medicines’ and EQRx’s stockholders. Each share of common stock of EQRx issued and outstanding immediately prior to the merger will be converted into the right to receive 0.1112 shares of common stock of Revolution Medicines. If the transaction is completed, Revolution Medicines expects to issue approximately 55 million shares of its common stock in connection with the merger (excluding assumed warrants and earn-out shares). The company estimates that the acquisition will add approximately $1.1 billion in net cash proceeds, after estimated post-closing EQRx wind-down and transition costs, or approximately $20 per share of common stock to be issued with the merger.
"Collectively, the clinical data presented on RMC-6236 and RMC-6291 demonstrate that these two investigational drugs have significant anti-tumor activity across dose levels that have been generally well tolerated in patients with common cancers harboring one of the four most common oncogenic RASG12 mutations. The overwhelmingly positive reaction our team heard from clinical investigators further validates the differentiation of our RAS(ON) Inhibitor platform and clearly supports continued investment in these compounds as monotherapy and/or in combination regimens," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "With the anticipated closing of the EQRx acquisition this month, the infusion of a sizable quantum of capital will allow Revolution Medicines to advance plans designed to fully realize the potential of our RAS(ON) inhibitor investigational drugs as we seek to fulfill our vision of revolutionizing treatment for patients living with RAS-addicted cancers."

Clinical and Development Highlights

Investigational RAS(ON) Inhibitors
RMC-6236 (RASMULTI)
RMC-6236 is an oral, RAS-selective, first-in-class RASMULTI(ON) Inhibitor designed to treat patients with cancers driven by a wide range of common RAS mutations. Initially being developed as monotherapy, planning is underway to also evaluate RMC-6236 in doublet combinations with mutant-selective RAS(ON) Inhibitors as well as other combination treatments.

The ongoing Phase 1/1b monotherapy trial (NCT05379985) is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6236 in patients with advanced solid tumors harboring select KRASG12 mutations, including G12D, G12V and G12R and was recently expanded to include G13 and Q61 mutations. A maximum tolerated dose has not yet been defined and dose optimization is ongoing.
The company is planning a global, randomized Phase 3 study comparing RMC-6236 against docetaxel in patients with previously treated RAS-mutated NSCLC who have been treated with immunotherapy and platinum-containing chemotherapy. The study design will be finalized after regulatory feedback. The study is expected to start in 2024.
The company is also designing a potential global randomized Phase 3 trial comparing RMC-6236 against a physician’s choice of chemotherapy regimens in patients with previously treated RAS-mutated PDAC. Future study decisions will be made after additional patient follow-up regarding durability of disease control and dose optimization and regulatory feedback. The company believes the study could potentially be initiated in 2024.
A Phase 1/1b clinical trial to evaluate the combination of RMC-6236 and RMC-6291 is currently recruiting patients. Planning is also underway for additional studies of RMC-6236 in combination with standard of care therapies, including immunotherapy and chemotherapy.
RMC-6291 (RASG12C)
RMC-6291, an oral, covalent inhibitor of RASG12C(ON) designed to treat patients with cancers driven by the KRASG12C mutant, is the first of the company’s mutant-selective RAS(ON) Inhibitors to enter clinical development and the first reported clinical-stage inhibitor of KRASG12C that uses a highly differentiated mechanism of action compared to first-generation KRASG12C(OFF) inhibitors. The ongoing Phase 1/1b monotherapy trial (NCT05462717) is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6291 in patients with advanced KRASG12C mutant solid tumors. A maximum tolerated dose has not yet been defined and dose optimization is ongoing.

In addition to the Phase 1/1b combination study of RMC-6291 and RMC-6236, planning is underway for studies to evaluate RMC-6291 in combination with standard of care therapies, including immunotherapy and chemotherapy.
RMC-9805 (RASG12D)
RMC-9805 is an oral, selective, covalent inhibitor of RASG12D(ON), the most common driver of RAS-addicted human cancers, predominantly among patients with PDAC, NSCLC or CRC. The company believes RMC-9805 is the first oral and covalent inhibitor of RASG12D.

The Phase 1/1b trial (NCT06040541) is an ongoing multicenter, open-label, dose-escalation and dose-expansion study of RMC-9805 in patients with advanced solid tumors harboring the KRASG12D mutation. The primary objectives of the study are to evaluate safety and tolerability, and to inform the recommended Phase 2 dose and schedule for the compound.
RAS Innovation Engine
Beyond the first wave of clinical-stage RAS(ON) Inhibitors, the company continues expanding its pipeline of RAS(ON) Inhibitor candidates.

RAS(ON) Inhibitor development candidates include RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C).
The company continues drug discovery efforts in RAS(ON) Inhibitor pipeline expansion programs focused on RAS mutation hotspots including G12R, G13D and other important targets.
Third Quarter 2023 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $813.2 million as of September 30, 2023, compared to $644.9 million as of December 31, 2022. The increase was primarily attributable to the company’s public equity offering in March 2023.

Revenue: Total revenue was zero for the quarter ended September 30, 2023, compared to $3.4 million for the quarter ended September 30, 2022.

R&D Expenses: Research and development expenses were $107.7 million for the quarter ended September 30, 2023, compared to $69.5 million for the quarter ended September 30, 2022. The increase was primarily due to an increase in clinical trial and clinical supply manufacturing expenses for RMC-6236 and RMC-6291, research expenses associated with the company’s pre-clinical portfolio, an increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation.

G&A Expenses: General and administrative expenses were $15.5 million for the quarter ended September 30, 2023, compared to $10.4 million for the quarter ended September 30, 2022. The increase was primarily due to an increase in stock-based compensation and an increase in personnel-related expenses related to additional headcount.

Net Loss: Net loss was $108.4 for the quarter ended September 30, 2023, compared to net loss of $73.3 million for the quarter ended September 30, 2022.

2023 Financial Guidance
Revolution Medicines is updating its projected full year 2023 GAAP net loss to be between $385 and $415 million, which includes estimated non-cash stock-based compensation expense of $45 million and $50 million. Based on the company’s current operating plan, the company projects current cash, cash equivalents and investments can fund planned operations into 2025. The Company’s financial guidance excludes the financial impact of the proposed EQRx transaction.

Webcast
Revolution Medicines will host a webcast this afternoon, November 6, 2023, at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time). To listen to the live webcast, or access the archived webcast, please visit: View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

On November 6, 2023 Protalix BioTherapeutics, Inc. (NYSE American: PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the third quarter ended September 30, 2023 and provided a business update on recent regulatory, clinical and corporate developments (Press release, Protalix, NOV 6, 2023, View Source [SID1234637045]).

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"We continued our efforts this quarter towards turning Protalix into a fully-sustainable biopharmaceutical company with a growing pipeline of differentiated proprietary assets. With the approval of Elfabrio by the U.S. FDA and the European Medicines Agency earlier this year, we are pleased to see our commercial partner Chiesi Global Rare Diseases hit the ground, both in the United States and the European Union. Additionally, Chiesi is continuing to position Elfabrio for future growth with additional approvals worldwide," said Dror Bashan, Protalix’s President and Chief Executive Officer. "Our strong balance sheet coupled with our growing revenue stream allows us to focus on the continued development of our growing pipeline of assets, including PRX-115, our recombinant PEGylated uricase in development for the potential treatment of severe gout. We are continuing to enroll patients in our Phase I clinical trial evaluating the safety, pharmacokinetics, pharmacodynamics and immunogenicity of PRX-115, and look forward to continuing to progress this product candidate forward, Mr. Bashan continued. "We are proud of our achievements and look forward to an exciting future as a company with a proven platform and two approved drugs, a rich pipeline of product candidates in lucrative markets, a world-class team of dedicated employees, strong financial support with a solid balance sheet and an increasing stream of revenues."

2023 Third Quarter and Recent Business Highlights

Regulatory Advancements

The Company, together with its development and commercialization partner, Chiesi Global Rare Diseases (Chiesi), a business unit of the Chiesi Group, continued to attain marketing authorizations around the world for Elfabrio (pegunigalsidase alfa) for the treatment of adult patients with Fabry disease. Elfabrio, a PEGylated enzyme replacement therapy (ERT), is a recombinant human α-Galactosidase-A enzyme expressed in plant-cell culture that is designed to provide a long half-life.

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On August 15, 2023, Chiesi announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization for Elfabrio in Great Britain for long-term enzyme replacement therapy in adult patients with a confirmed diagnosis of Fabry disease.

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On September 11, 2023, Swissmedic, the national authorization and supervisory authority for drugs and medical products in Switzerland, announced the approval of Elfabrio in Switzerland for long-term enzyme replacement therapy in adult patients with a confirmed diagnosis of Fabry disease.

Clinical Developments

The Company continued to advance its First in Human (FIH) phase I clinical trial of PRX–115, a recombinant PEGylated uricase product candidate under development as a potential treatment for severe gout. To date, 32 patients have been dosed in the trial. The FIH trial is a double-blind, placebo-controlled, single ascending dose study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of PRX-115

in up to 56 patients with elevated uric acid levels (>6.0 mg/dL) and no previous exposure to PEGylated uricase. The study is being conducted at New Zealand Clinical Research (NZCR) under the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the Health and Disability Ethics Committee (HDEC) guidelines. We expect to announce top-line results from this study in mid-2024.

Corporate Developments

On September 14, 2023, Eliot Richard Forster, Ph.D. joined the Company’s Board of Directors as its Chairman, replacing former Chairman Zeev Bronfeld, who retired for personal reasons. In addition to his role as Chairman, Dr. Forster is serving as an independent director on the Company’s Nominating Committee.

Third Quarter 2023 Financial Highlights

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The Company recorded revenues from selling goods of $10.2 million during the three months ended September 30, 2023, an increase of $1.4 million, or 16%, compared to revenues of $8.8 million for the three months ended September 30, 2022. The increase resulted primarily from an increase of $3.0 million in sales to Chiesi, following the approvals by the FDA and the EMA of Elfabrio, and of $0.6 million in sales to Brazil, partially offset by a $2.2 million decrease in sales to Pfizer.

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The Company recorded revenues from license and R&D services of $0.2 million for the three months ended September 30, 2023, a decrease of $5.2 million, or 96%, compared to revenues of $5.4 million for the three months ended September 30, 2022. Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements. As of March 1, 2023, sponsorship of the extension studies was transferred to Chiesi, and Chiesi is now administering all open label extension studies.

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Cost of goods sold was $4.9 million for the three months ended September 30, 2023, a decrease of $2.2 million, or 31%, from cost of goods sold of $7.1 million for the three months ended September 30, 2022. The decrease in cost of goods sold was primarily the result of the decrease in sales to Pfizer, partially offset by an increase in sales of Elfabrio to Chiesi and of Elelyso to Brazil.

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For the three months ended September 30, 2023, the Company’s total research and development expenses were approximately $3.7 million comprised of approximately $1.0 million of subcontractor-related expenses, approximately $1.9 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.6 million of other expenses. For the three months ended September 30, 2022, our total research and development expenses were approximately $7.4 million comprised of approximately $4.9 million in subcontractor-related expenses, approximately $1.7 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.6 million of other expenses. Total decrease in research and developments expenses was $3.7 million, or 50%, compared to the three months ended September 30, 2022. The decrease in research and development expenses primarily resulted from the completion of our Fabry clinical program and the regulatory processes related to the Biologics License Application (BLA) and Marketing Authorization Application (MAA) review of Elfabrio by the applicable regulatory agencies.

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Selling, general and administrative expenses were $3.7 million for the three months ended September 30, 2023, an increase of $0.9 million, or 32%, compared to $2.8 million for the three months ended September 30, 2022. The increase resulted primarily from an increase of approximately $0.6 million in salary and related expenses due to one-time cash bonuses and an increase in share-based compensation.

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Financial income, net was $0.2 million for the three months ended September 30, 2023, compared to financial expenses, net of $0.4 million for the three months ended September 30, 2022. The change resulted primarily from an increase of $0.3 million in interest income.

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In the three months ended September 30, 2023, the Company recorded income taxes of approximately $0.1 million which were primarily the result of the provision for current taxes in respect of Section 174 of the U.S. Tax Cuts and Jobs Act, which was enacted in December 2017.

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Cash, cash equivalents and short term bank deposits were approximately $41.0 million at September 30, 2023.

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Net loss for the three months ended September 30, 2023 was approximately $1.9 million, or $0.03 per share, basic, and $0.04 per share, diluted, compared to a net loss of $3.6 million, or $0.07 per share, basic and diluted, for the same period in 2022.

Conference Call and Webcast Information
The Company will host a conference call today, November 6, 2023, at 8:30 a.m. EST, to review the regulatory, clinical and corporate developments, which will also be available by webcast. To participate in the conference call, please dial the following numbers prior to the start of the call:

On November 6, 2023 PharmaMar (MSE:PHM) has reported receipt of a payment of $10 million from Janssen Products LP after reaching a commercial milestone for Yondelis (trabectedin) in the United States as defined in the licensing agreement (Press release, PharmaMar, NOV 6, 2023, View Source [SID1234637044]).

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In August 2019, PharmaMar entered into a new licensing agreement with Janssen, which replaced a 2001 licensing agreement, under which Janssen retained the right to sell and distribute, on an exclusive basis, Yondelis in the USA.

Today, Yondelis is approved in more than 70 countries for the treatment of Soft Tissue Sarcoma and in some of these countries for ovarian cancer as well.

On November 6, 2023 Orum Therapeutics ("Orum"), a clinical-stage private biotechnology company pioneering Dual-Precision Targeted Protein Degradation (TPD² ) and Targeted Protein Stabilization (TPS² ), reported that they have entered into a definitive agreement under which Bristol Myers Squibb has acquired Orum’s ORM-6151 program (Press release, Orum Therapeutics, NOV 6, 2023, View Source [SID1234637043]). ORM-6151 is a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader that has received the FDA’s clearance for Phase 1 for the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndromes.

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"We believe this agreement with Bristol Myers Squibb, a global leader in cancer with a strong legacy in protein degradation, validates Orum’s unique Dual-Precision Targeted Protein Degradation approach, which we pioneered to improve the therapeutic window and realize the full potential of targeted protein degraders through precision delivery to cancer cells via antibody drug conjugates," said Sung Joo Lee, Ph.D., CEO of Orum Therapeutics. "We are excited that Bristol Myers Squibb has acquired our ORM-6151 program with proprietary GSPT1 degraders, first-in-class targeted protein degraders with the potential to make an impact for patients with cancer."

Under this transaction, Bristol Myers Squibb has acquired Orum’s ORM-6151 program for an upfront payment of $100 million, and Orum Therapeutics is eligible to receive milestone payments for a total deal value of $180 million. Further details were not disclosed.

Perella Weinberg Partners acted as financial advisor, and Sterne Kessler Goldstein & Fox, and Skadden, Arps, Slate, Meagher & Flom LLP served as legal advisor to Orum Therapeutics.

About Orum’s GSPT1 Platform Using the TPD² Approach

Orum’s GSPT1 platform uses the company’s unique Dual-Precision Targeted Protein Degradation (TPD²) approach to build novel targeted protein degraders combined with the precise tumor cell delivery mechanisms of antibodies to generate innovative, first-in-class, tumor-selective TPDs for the treatment of cancer. Orum has developed new molecular glue degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, the payloads are designed to be delivered specifically to cancer cells and degrade the intracellular target protein GSPT1 and cause tumor cell death.