On May 9, 2022 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing a first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, reported financial results for the first quarter of 2022, including current and projected financial resources (Press release, Geron, MAY 9, 2022, View Source [SID1234613917]).

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"This quarter, we continued to build on the momentum from our clinical execution throughout 2021, with our first Phase 3 data readout expected in just eight months. We believe that if the Phase 3 IMerge trial in lower risk MDS confirms similar depth, breadth and durability of transfusion independence, and safety, observed in our Phase 2 study, imetelstat could represent a significant treatment advance for these heavily transfusion-burdened patients," said John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer. "Separately, we are advancing our IMpactMF Phase 3 refractory MF trial by continuing to open clinical sites around the world, which we expect to enable a potential interim analysis in 2024. We are also executing on our IMproveMF Phase 1 study, which has recently started. This study will allow us to potentially demonstrate safety and efficacy of combination therapy with imetelstat and ruxolitinib in the frontline MF setting."

Dr. Scarlett continued: "The successful financing in April adds to our current financial resources, as well as provides access to additional capital upon the potential exercise of warrants in the future. We expect these current and projected financial resources will be sufficient for our projected operations through the end of 2023, including planned key regulatory milestones and pre-commercial activities. In addition, this extended cash runway provides us the opportunity to thoughtfully and broadly explore multiple business strategies, including partnering and financing options, to optimize the value of imetelstat for patients and shareholders."

Current and Projected Financial Resources

As of March 31, 2022, the Company had $178.0 million in cash and marketable securities. In April 2022, the Company completed an underwritten public offering of 53,333,334 shares of Geron common stock and a pre-funded warrant to purchase 18,095,238 shares of Geron common stock (pre-funded warrant), together with accompanying warrants to purchase 35,714,286 shares of Geron common stock (stock purchase warrants). The combined public offering price of the common stock and accompanying stock purchase warrants was $1.05 per share. The combined public offering price of the pre-funded warrant and accompanying stock purchase warrant was $1.049 per share. The net cash proceeds from this offering are approximately $70 million, after deducting the underwriting discount and other offering expenses payable by the Company and excludes any future proceeds from the exercise of the pre-funded warrant or the stock purchase warrants. The stock purchase warrants have an exercise price of $1.45 per share and expire five years from the date of issuance; however, such term will be shortened upon achievement of a regulatory milestone.

Under current planning assumptions, the Company projects its existing capital resources, including the net proceeds from the public offering completed in April 2022, and projected future proceeds of up to $124.3 million from the exercise of currently outstanding warrants will be sufficient to fund Geron’s projected level of operations, which includes preparatory activities for potential U.S. commercial launch of imetelstat in lower risk MDS, until the end of 2023.

First Quarter 2022 Results

For the first quarter of 2022, the Company reported a net loss of $30.1 million, or $0.09 per share, compared to $27.8 million, or $0.09 per share, for the same period in 2021.

Revenues for the first quarter of 2022 were $123,000 compared to $137,000 for the same period in 2021. Royalty revenues in 2022 and 2021 primarily reflect estimated royalties from sales of cell-based research products from the Company’s divested stem cell assets.

Total operating expenses for the first quarter of 2022 were $28.8 million compared to $28.6 million for the same period in 2021. Research and development expenses for the first quarter of 2022 were $22.1 million compared to $21.1 million for the same period in 2021. The increase in research and development expenses in the first quarter of 2022, compared to the same period in 2021, primarily reflects higher personnel-related costs for additional headcount. General and administrative expenses for the first quarter of 2022 were $6.7 million compared to $7.5 million for the same period in 2021. The decrease in general and administrative expenses in the first quarter of 2022, compared to the same period in 2021, primarily reflects the net result of reduced costs related to modernizing the internal infrastructure to support commercial launch and lower legal fees, partially offset by higher personnel-related expenses for additional headcount.

Interest income for the first quarter of 2022 was $112,000 compared to $173,000 for the same period in 2021. The decrease in interest income in the first quarter of 2022, compared to the same period in 2021, primarily reflects lower yields on the Company’s reduced marketable securities portfolio.

Interest expense for the first quarter of 2022 was $1.5 million compared to $743,000 for the same period in 2021. Currently, the Company has $50.0 million in principal debt outstanding.

Net other expense for the first quarter of 2022 was $56,000 compared to net other income of $1.2 million for the same period in 2021. During the first quarter of 2021, the Company sold all of its holdings in an equity investment resulting in a net realized gain of $1.2 million, including foreign currency translation adjustments.

Projected 2022 Financial Guidance Reaffirmed

For fiscal year 2022, under generally accepted accounting principles (GAAP), the Company continues to expect total operating expenses in the range of approximately $155 million to $165 million, which includes non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs and depreciation and amortization. The Company continues to expect non-GAAP total operating expenses for fiscal year 2022, which excludes estimated non-cash items such as: stock-based compensation expense, amortization of debt discounts and issuance costs and depreciation and amortization, in the range of approximately $140 million to $150 million.

The fiscal year 2022 financial guidance reflects costs to support: (a) preparatory activities for top-line results from the IMerge Phase 3 clinical trial and readiness for potential regulatory filings and commercialization of imetelstat in lower risk MDS; (b) continued conduct of IMerge and IMpactMF and commencement of new clinical studies associated with the imetelstat pipeline expansion strategy; (c) finalizing validation batches of imetelstat at contract manufacturers to enable future production of imetelstat for clinical and commercial purposes; (d) projected increases in headcount and (e) interest payments on outstanding debt.

As of March 31, 2022, the Company had 79 employees. The Company plans to grow to a total of approximately 90 to 100 employees by year-end 2022.

Conference Call

Geron will host a conference call at 4:30 p.m. ET on Monday, May 9, 2022 to review recent events and first quarter 2022 financial results.

A live webcast of the conference call and related presentation will be available on the Company’s website at www.geron.com/investors/events. An archive of the webcast will be available on the Company’s website for 30 days.

Participants may access the webcast by registering online using the following link: View Source Participants that are unable to register online can access the conference call via telephone by dialing domestically +1 (888) 330-2434 or internationally +1 (240) 789-2725. The conference ID is 67335.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

About IMerge Phase 3

IMerge Phase 3 is a double-blind, randomized, placebo-controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 170 transfusion dependent patients with Low or Intermediate-1 risk myelodysplastic syndromes (MDS), also referred to as lower risk MDS, who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, duration of TI and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

IMerge Phase 3 is fully enrolled and patient enrollment has been closed. For additional information about IMerge Phase 3, visit ClinicalTrials.gov/NCT02598661.

About IMpactMF

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis (MF) who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete remission, partial remission, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.

About IMproveMF

IMproveMF is a single arm, open label Phase 1 study to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of imetelstat in combination with ruxolitinib in patients with frontline myelofibrosis (MF), consisting of two parts. Part one will enroll up to 20 patients and is designed to identify a safe dose for the combination of imetelstat and ruxolitinib. Part two will also enroll approximately 20 patients and is designed to confirm the dose identified in part one.

On May 9, 2022 Inhibikase Therapeutics, Inc. (Nasdaq: IKT) (Inhibikase), a clinical-stage pharmaceutical company developing therapeutics to modify the course of Parkinson’s disease and related disorders, reported that it will report financial results for the first quarter ended March 31, 2022 on Monday, May 16, 2022, after the close of U.S. markets (Press release, Inhibikase Therapeutics, MAY 9, 2022, View Source [SID1234613916]). Following the announcement, the Company will host a conference call and webcast at 8:00 a.m. ET on Tuesday, May 17, 2022 to provide a corporate update and review the financial results.

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The conference call can be accessed by dialing 877-407-4018 (United States) or 201-689-8471 (International) with the conference code 13729218. A live webcast may be accessed using the link here, or by visiting the investors section of the Company’s website at www.inhibikase.com. After the live webcast, the event will be archived on Inhibikase’s website for approximately 90 days after the call.

On May 9, 2022 Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported its financial results for the first quarter ended March 31, 2022 (Press release, Syndax, MAY 9, 2022, View Source [SID1234613915]). In addition, the Company provided a clinical and business update.

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"Throughout the first quarter, we continued to realize significant progress advancing our two pivotal programs, for which we expect to report topline data starting in the first half of 2023," said Michael A. Metzger, Chief Executive Officer. "We firmly believe revumenib (SNDX-5613) is positioned to serve as a first-to-market and best-in-class menin inhibitor for patients with NPM1 and MLLr acute leukemias. We have also begun exploring its activity beyond use as a monotherapy agent through initiation of two new trials, including in combination with venetoclax-azacitidine for use as a frontline treatment, and in combination with chemotherapy for relapsed/refractory (R/R) disease. Beyond acute leukemias, we intend to assess revumenib’s (SNDX-5613) potential in additional areas where menin inhibition could have a strong therapeutic benefit, and we look forward to commencing a proof-of-concept clinical trial in patients with advanced colorectal cancer (CRC), a highly underserved area lacking effective therapeutic options, in the fourth quarter of the year."

"Additionally, enrollment continues in the ongoing global pivotal Phase 2 AGAVE-201 trial of axatilimab in chronic graft-versus-host disease (cGVHD), with topline data expected in the first half of 2023 and a potential Biologic License Application (BLA) filing in 2023. Supported by recent receipt of Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA), we believe axatilimab has the potential to play a meaningful role in the cGVHD treatment landscape. Furthermore, as previously announced, we are committed to unlocking axatilimab’s full potential in additional fibrotic diseases where the monocyte-macrophage lineage plays a vital role, and remain on track to commence a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) in the fourth quarter of this year."

Recent Pipeline Progress and Anticipated Milestones

Revumenib (SNDX-5613)

The pivotal Phase 2 portion of AUGMENT-101 is ongoing and the Company continues to expect completion of enrollment in at least one of the three pivotal cohorts later this year. The trials are expected to enroll a total of 64 adult and up to 10 pediatric patients across each of three distinct trial populations: patients with NPM1 mutant acute myeloid leukemia (AML), patients with MLLr AML, and patients with MLLr acute lymphocytic leukemia (ALL). Based on discussions with the U.S. FDA, AUGMENT-101 may serve as the basis for regulatory filings in each of the three distinct populations. The Company expects to receive initial topline data from the trials starting in the first half of 2023, with the potential for the first New Drug Application filing in 2023.
Two additional trials, BEAT-AML and AUGMENT-102, are now underway to assess the safety, tolerability, and preliminary anti-leukemic efficacy of revumenib (SNDX-5613) and establish an appropriate Phase 2 dose. BEAT-AML is a front-line combination trial of revumenib (SNDX-5613) with venetoclax and azacitidine being conducted as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial. The primary endpoint of the Phase 1 portion of the BEAT-AML trial is to determine the recommended Phase 2 dose of the combination. The Company also initiated a trial in combination with chemotherapy in patients with R/R NPM1 or MLLr acute leukemias, known as AUGMENT-102. The primary endpoint of AUGMENT-102 will assess the safety, tolerability, and recommended Phase 2 dose criteria. Topline data from the trials are expected beginning in 2023.
The Company reported it intends to initiate a proof-of-concept clinical trial to evaluate revumenib (SNDX-5613) in patients with unresectable metastatic microsatellite stable CRC, which represents the second leading cause of cancer death in the U.S. with an estimated incidence of over 55,000 patients per year1,2. Activation of the Wnt/b-catenin signaling pathway is believed to be a key initiating step and growth driver for the majority of CRC tumors. The menin-MLL1 protein complex has recently been shown to regulate b-catenin activity and in preclinical models, disrupting this complex through menin inhibition blocks growth of Wnt/b-catenin driven CRC tumors. The Company is expected to commence the trial in the fourth quarter of 2022.
Axatilimab

The Company reported that the U.S. FDA has granted FTD to axatilimab for the treatment of patients with cGVHD after failure of two or more lines of systemic therapy. FTD is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need, enabling drugs to reach patients earlier.
Enrollment is ongoing in the Company’s global pivotal Phase 2 AGAVE-201 trial of axatilimab in patients with cGVHD. The trial is evaluating the safety and efficacy of three doses and schedules of axatilimab. The primary endpoint will assess objective response rate based on the 2014 NIH consensus criteria for cGVHD, with key secondary endpoints including duration of response and improvement in modified Lee Symptom Scale score. The Company remains on track to report topline data in the first half of 2023, with the potential for a BLA filing in 2023.
First Quarter 2022 Financial Results

As of March 31, 2022, Syndax had cash, cash equivalents and short-term investments of $397.9 million and 59.0 million shares and share equivalents issued and outstanding. This includes 4.0 million pre-funded warrants.

First quarter 2022 research and development expenses increased to $30.0 million from $21.9 million for the prior year period. The increase was primarily due to increased clinical and manufacturing activities.

General and administrative expenses for the first quarter 2022 increased to $6.8 million from $5.7 million for the prior year period. The increase is primarily due to increased compensation and professional fees.

For the three months ended March 31, 2022, Syndax reported a net loss attributable to common stockholders of $37.2 million or $0.63 per share compared to a net loss attributable to common stockholder of $27.7 million or $0.54 per share for the prior year period.

Financial Update and Guidance

For the second quarter of 2022, research and development expenses are expected to be $30 to $35 million, and total operating expenses are expected to be $38 to $42 million. For the full year of 2022, research and development expenses are expected to be $130 to $140 million, and total operating expenses are expected to be $160 to $170 million.

Conference Call and Webcast

In connection with the earnings release, Syndax’s management team will host a conference call and live audio webcast at 4:30 p.m. ET today, Monday, May 9, 2022.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website at www.syndax.com. Alternatively, the conference call may be accessed through the following:

For those unable to participate in the conference call or webcast, a replay will be available for 30 days on the Investors section of the Company’s website, www.syndax.com.

On May 9, 2022 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, reported preliminary financial results for the first quarter of 2022, and associated Company developments (Press release, Supernus, MAY 9, 2022, View Source [SID1234613914]).

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Qelbree Launch Update

Total IQVIA prescriptions were 47,324 in the first quarter of 2022, an increase of 38% compared to total prescriptions of 34,328 in the fourth quarter of 2021. In March 2022, the most recent month available, total prescriptions reached 18,380.
Qelbree continues to expand its base of prescribers, with approximately 6,900 prescribers in the first quarter of 2022, up from 5,600 prescribers from the fourth quarter of 2021.
Continued progress in securing and improving managed care coverage.
At the end of April 2022, the U.S. Food and Drug Administration (FDA) approved Qelbree for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults. Supernus is expecting to launch Qelbree for adult patients by the end of May 2022. According to recent IQVIA Xponent 52-week data, prescriptions for the adult market represented approximately 68% of the total ADHD market.
Product Pipeline Update

SPN-830 (apomorphine infusion device) – Continuous treatment of motor fluctuations ("off" episodes) in Parkinson’s disease (PD)

The Company will continue to work closely with the FDA as it reviews the New Drug Application (NDA) resubmission for SPN-830 for the continuous treatment of motor fluctuations ("off" episodes) in Parkinson’s disease. The Company is preparing for the commercial launch of SPN-830 in the first quarter of 2023, assuming timely approval by the FDA. The FDA has established a PDUFA target action date in early October 2022.
SPN-820 – Novel first-in-class activator of mTORC1

The Company continues to enroll patients in a Phase II multi-center, randomized double-blind placebo-controlled parallel design study of SPN-820 in adults with treatment-resistant depression. The study will examine the efficacy and safety of SPN-820 over a course of five weeks of treatment in approximately 270 patients. The primary outcome measure is the change from baseline to end of treatment period on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score, a standard depression rating scale.
SPN-817 – A novel product candidate for the treatment of epilepsy

An open-label Phase II clinical study of SPN-817 in patients with treatment-resistant seizures is expected to start in the second half of 2022.
Financial Highlights

Net Product Sales

For the first quarter 2022, net product sales were $147.5 million, a 15% increase over $128.4 million for the same period in 2021. The increase was primarily due to net product sales of GOCOVRI from the Adamas acquisition in November 2021 (Adamas Acquisition) and growth in net product sales of Qelbree that was launched in the second quarter of 2021.

(1) Includes net product sales of MYOBLOC, XADAGO and Osmolex ER.

Operating earnings (GAAP and non-GAAP)

First quarter 2022 operating earnings (GAAP) was $2.0 million, as compared to $13.2 million for the same period in 2021. The decrease is primarily due to amortization of acquired intangible assets from the Adamas Acquisition. First quarter 2022 adjusted operating earnings (non-GAAP) was $28.0 million, an increase of 11% compared to $25.2 million in the first quarter of 2021.

Reconciliation of GAAP to Non-GAAP Adjustments

An itemized reconciliation between operating earnings on a GAAP basis and operating earnings on a non-GAAP basis is as follows:

Non-GAAP operating earnings adjusts for non-cash items including amortization of intangible assets, share-based compensation expense, change in fair value of contingent consideration, and depreciation. Included in the amortization of intangible assets for the first quarter of 2022 is amortization of acquired intangible assets from the Adamas Acquisition in November 2021.

Net earnings (GAAP)

First quarter 2022 net earnings and diluted earnings per share (GAAP) were $25.6 million and $0.43, respectively, as compared to $5.7 million, or $0.11 per diluted share, in the same period in 2021.

Cash, cash equivalents and marketable securities

At March 31, 2022, the Company’s cash, cash equivalents, current and long-term marketable securities are approximately $437.5 million, compared to $458.8 million as of December 31, 2021. This decrease is primarily due to milestone payments associated with the 2020 USWM acquisition and transition expense payments related to the Adamas acquisition, partially offsetting cash generated from operations.

Full Year 2022 Financial Guidance (GAAP)

For full year 2022, the Company reiterates its prior financial guidance as set forth below:

(1) Includes net product sales and royalty revenue.
(2) Includes amortization of intangible assets and contingent consideration expense (gain).

Full Year 2022 Financial Guidance – GAAP to Non-GAAP Adjustments

An itemized reconciliation between projected operating earnings on a GAAP basis and projected operating earnings on a non-GAAP basis is as follows:

This press release contains a financial measure, non-GAAP operating earnings, which does not comply with United States generally accepted accounting principles (GAAP). The non-GAAP financial measure should be considered in addition to, not as a substitute for or in isolation from, or superior to measures prepared in accordance with GAAP. Non-GAAP operating earnings adjust for non-cash share-based compensation expense, depreciation and amortization, and accretion of contingent consideration, and for factors that are unusual, non-recurring or unpredictable, and exclude those costs, expenses, and other specified items presented in the reconciliation tables in this press release. We believe the use of non-GAAP operating earnings is useful supplemental information to investors regarding the Company’s results of operations and assist management, analysts, and investors in evaluating the performance of the business. There are limitations associated with the use of non-GAAP financial measures. Including such measures may not be entirely comparable to similarly titled measures used by other companies, may not reflect all items of income and expense, as applicable, that affect our operations, potential differences among calculation methodologies, may differ from the non-GAAP information used by other companies, including peer companies, and therefore comparability may be limited. We mitigate these limitations by reconciling the non-GAAP financial measure to the most comparable GAAP financial measure. Investors are encouraged to review the reconciliation. The Company’s 2022 financial guidance is also being provided on both a reported and a non-GAAP basis.

Conference Call Details

Supernus will host a conference call and webcast today, May 9, 2022, at 4:30 p.m. Eastern Time to discuss these results.

Please refer to the information below for conference call dial-in information and webcast registration. Callers should dial in approximately 10 minutes prior to the start of the call.

Following the live call, a replay will be available on the Company’s website, www.supernus.com, under "Investor Relations".

On May 09, 2022 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 March 31, 2022 and provided an update on corporate progress (Press release, Revolution Medicines, MAY 9, 2022, View Source [SID1234613913]).

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"At Revolution Medicines, we are passionately pursuing our mission to outsmart cancer with a disruptive portfolio of RAS(ON) Inhibitors in development for patients with RAS-addicted cancers," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "With compounds RMC-6236 and RMC-6291 expected to enter the clinic this year and a pipeline of other compounds behind them, we are advancing a wave of RAS(ON) Inhibitor drug candidates that could address the majority of these cancers that lack effective targeted drugs.

"Concurrently, we continue clinical evaluation of the class-leading RAS Companion Inhibitors RMC-4630 and RMC-5552 that are intended as combination agents to maximize patient benefit. Our integrated pipeline of RAS(ON) Inhibitors and RAS Companion Inhibitors enables the science-driven treatment strategies we have designed to overcome common causes of treatment failure."

First Quarter 2022 Corporate Highlights

RAS(ON) Inhibitors

RMC-6236 (RASMULTI)

RMC-6236 is a potent, oral, RAS(ON)-selective tri-complex inhibitor designed to treat patients with cancers driven by a variety of RAS mutations, including KRASG12D, KRASG12V and KRASG12R. Additionally, RMC-6236 may be deployed as a RAS Companion Inhibitor in combination with mutant-selective RAS(ON) Inhibitors.

The company has submitted an Investigational New Drug (IND) application for RMC-6236 to the U.S. Food and Drug Administration (FDA) and expects to announce dosing of the first patient in a monotherapy dose-escalation study in mid-2022. The company anticipates providing evidence of first-in-class single agent activity for RMC-6236 in 2023.
RMC-6291 (KRASG12C)

RMC-6291 is a potent, oral, selective, covalent inhibitor of KRASG12C(ON) with a differentiated preclinical profile. It is designed to serve patients with cancers driven by the KRASG12C mutant.

The company remains on track to submit an IND application for RMC-6291 to the FDA in the first half of 2022 and expects to announce dosing of the first patient in its monotherapy dose-escalation study in the second half of 2022. The company anticipates disclosing preliminary evidence of superior activity for RMC-6291 in 2023.
RMC-9805 (KRASG12D)

RMC-9805 is an oral, selective, covalent inhibitor of KRASG12D(ON), the primary tumor driver for more than 50,000 new patients annually in the United States, predominantly patients with colorectal (CRC), pancreatic or non-small cell lung cancer (NSCLC). The company believes this compound is the first covalent oral inhibitor of KRASG12D.

The company expects to announce dosing of the first patient in a monotherapy dose- escalation study of RMC-9805 in mid-2023.
RMC-8839 (KRASG13C)

RMC-8839 is an oral, selective, covalent inhibitor of KRASG13C(ON). The company believes RMC-8839 is the first compound to directly inhibit KRASG13C, an important therapeutic target primarily for NSCLC and select CRC patients unserved by a targeted RAS inhibitor.

The company expects to announce dosing of the first patient in a monotherapy dose-escalation study of RMC-8839 in late 2023 or early 2024.
RAS Innovation Engine

The company is leveraging its innovative tri-complex platform and advanced cancer discovery capabilities to identify additional orally bioavailable, tri-complex RAS(ON) Inhibitors to target RAS variants driving RAS-addicted cancers that are unserved by a targeted RAS inhibitor.

The company is pursuing multiple pipeline expansion programs focused on RAS mutation hotspots G12 (e.g., G12V and G12R), G13 (e.g., G13D) and Q61.
The company is on track to nominate a fifth RAS(ON) Inhibitor development candidate in the second half of 2022.
AACR Highlights

The company demonstrated sector leadership in RAS pathway targeting with seven oral presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022. The presentations highlighted key themes in the company’s multi-part approach to outsmarting cancer.

RAS(ON) Inhibitors demonstrate compelling monotherapy activity in diverse preclinical models of genetically defined RAS cancers.
RMC-6236 achieved significant monotherapy responses in mouse clinical trials in KRASG12-mutant NSCLC, CRC, and pancreatic cancer models.
RMC-6291 demonstrated superiority over adagrasib (MRTX849) in a head-to-head mouse clinical trial in KRASG12C NSCLC models.
Selective inhibitor of KRASQ61H(ON) drove significant tumor regressions in a KRASQ61H pancreatic cancer model.
RAS(ON) Inhibitors can be combined with RAS Companion Inhibitors to improve anti-tumor activity in models that are less sensitive to RAS(ON) Inhibitor monotherapy.
RMC-6236 deployed as a RAS Companion Inhibitor in combination with RMC-6291 demonstrated enhanced anti-tumor activity in KRASG12C NSCLC and CRC models that were refractory to single agent treatments.
RAS(ON) Inhibitors as monotherapies reverse the immune-suppressive tumor microenvironment in RAS-driven cancers and can unlock profound anti-tumor immunity when combined with immune system modulators such as PD-1 checkpoint inhibitors.
RAS Companion Inhibitors

RMC-4630 (SHP2)

RMC-4630 is a potent, oral small molecule that is designed to selectively inhibit the activity of SHP2, an upstream cellular protein that plays a central role in modulating cell survival and growth by facilitating RAS pathway signaling. RMC-4630 (also known as SAR442720) is progressing in a clinical program under the company’s partnership with Sanofi, the company’s global SHP2 development and commercialization partner.

RMC-4630 and KRASG12C Inhibitor Lumakras (sotorasib)

CodeBreaK 101c: Phase 1b trial sponsored by Amgen Inc. evaluating RMC-4630 in combination with Amgen’s KRASG12C(OFF) inhibitor, sotorasib, in patients with advanced solid tumors is progressing. Amgen recently announced that initial data from this trial were submitted to a medical congress taking place in the late summer.
RMC-4630-03: Global Phase 2 study of RMC-4630 in combination with sotorasib in patients with advanced NSCLC with a KRASG12C mutation who have failed prior standard therapy and who have not been previously treated with a RAS inhibitor is progressing. Revolution Medicines is sponsoring the trial as a complement to the CodeBreaK 101c trial under its global partnership with Sanofi, and in collaboration with Amgen, which is supplying sotorasib to trial sites globally. Revolution Medicines expects to complete enrollment of this study in the second half of 2022 and to provide preliminary evidence of clinical benefit of RMC-4630 as a RAS Companion Inhibitor in 2022. Additional evidence of clinical benefit of this compound is expected to be provided in 2023.
RMC-4630 and KRASG12C Inhibitor adagrasib

Sanofi is planning a Phase 1/2 dose escalation and expansion study under its global SHP2 partnership with Revolution Medicines, and in collaboration with Mirati. The study will evaluate RMC-4630 in combination with adagrasib (MRTX849), Mirati’s KRASG12C inhibitor, in patients with previously treated NSCLC who harbor KRASG12C mutations. This study expands the evaluation of the potential benefit of adding RMC-4630 in this class of KRASG12C(OFF) inhibitors.
RMC-4630 and PD-1 Inhibitor KEYTRUDA (pembrolizumab)

TCD16210: Phase 1 trial sponsored by Sanofi evaluating RMC-4630 in combination with KEYTRUDA (pembrolizumab), a PD-1 inhibitor is progressing. Sanofi is treating patients in an expansion cohort evaluating this combination in first-line treatment for patients with PDL-1 positive NSCLC.
RMC-5552 (mTORC1/4EPB1)

RMC-5552 is a potent, first-in-class, bi-steric mTORC1-selective inhibitor designed to suppress phosphorylation and inactivation of 4EBP1 for cancers with hyperactive mTORC1 signaling, including certain RAS-addicted cancers. The company intends to combine RMC-5552 with RAS(ON) Inhibitors in patients with cancers harboring RAS/mTOR pathway co-mutations.

An ongoing Phase 1/1b clinical trial evaluating RMC-5552 monotherapy is progressing. In January 2022, the company reported preliminary evidence of clinical activity, and dose optimization is underway to prepare for combination studies in RAS cancers. The company anticipates disclosing additional evidence of single agent activity in 2023.
The company aims to evaluate RMC-5552 in combination with RAS(ON) Inhibitors in patients carrying both RAS and mTOR pathway mutations, representing approximately 30,000 new patients per year in the United States.
First Quarter 2022 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $518.8 million as of March 31, 2022, compared to $577.1 million as of December 31, 2021. The decrease was primarily attributable to net loss for the quarter ended March 31, 2022.

Revenue: Total revenue, consisting of revenue from the company’s collaboration agreement with Sanofi, was $7.6 million for the quarter ended March 31, 2022, compared to $10.2 million for the quarter ended March 31, 2021. The decrease was related to lower reimbursed development costs under our collaboration agreement with Sanofi.

R&D Expenses: Research and development expenses were $56.5 million for the quarter ended March 31, 2022, compared to $40.9 million for the quarter ended March 31, 2021. The increase was primarily due to an increase in research expenses associated with the company’s pre-clinical research 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 $9.0 million for the quarter ended March 31, 2022, compared to $6.7 million for the quarter ended March 31, 2021. 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 $57.6 million for the quarter ended March 31, 2022, compared to net loss of $37.2 million for the quarter ended March 31, 2021.

2022 Financial Guidance

Revolution Medicines reiterates full year 2022 GAAP net loss to be between $260 million and $290 million, which includes estimated non-cash stock-based compensation expense of $35 million to $40 million.

Conference Call

Revolution Medicines will host a conference call and webcast this afternoon, May 9, 2022, at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time).

To listen to the conference call, please dial (833) 423-0425 (U.S.) or + 1 (918) 922-3069 (international), provide conference ID: 6994747 and request the Revolution Medicines conference call. 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.