On february 27, 2023 Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT), a leading late-stage biotechnology company advancing an integrated and sustainable pipeline of genetic therapies for rare disorders with high unmet need, reported financial and operational results for the fourth quarter and year ended December 31, 2022 (Press release, Rocket Pharmaceuticals, FEB 27, 2023, View Source [SID1234627744]).

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"Rocket closed 2022 with positive results across four clinical gene therapy programs spanning both our AAV cardiology and LV hematology therapeutic areas in an unprecedented fashion for a gene therapy company, validating our approach to strong science and R&D, carefully selected assets and smart execution. We are thrilled to begin 2023 with the FDA recently granting RMAT designation to RP-A501 for Danon Disease, validating the strength of our results and underscoring RP-A501’s potential as a transformative therapy for Danon patients," said Gaurav Shah, M.D., Chief Executive Officer of Rocket Pharma.

Dr. Shah continued, "At the same time, we expanded our leadership position in AAV cardiac gene therapy with the recent unveiling of compelling preclinical proof of concept for RP-A601 for the treatment of PKP2 arrhythmogenic cardiomyopathy (PKP2-ACM) and addition of the BAG3-associated dilated cardiomyopathy (DCM) asset following the acquisition of Renovacor. Taken together, these two diseases along with Danon Disease affect more than 100,000 patients in the U.S. and EU. Further, our LV hematology portfolio delivered stellar results as we now advance towards our first regulatory filings for Leukocyte Adhesion Deficiency (LAD-I) in the second quarter of 2023 and Fanconi Anemia (FA) in the fourth quarter of 2023, and subsequent commercialization."

"I am also pleased that we brought in additional funds of $197.7 million in 2022. We begin this year in a strong financial position to execute on near and long-term milestones, anticipating that our cash runway of approximately $400 million will fund operations through 2024," said Dr. Shah. "I am grateful to our growing Rocket team of multi-disciplinary experts, scientific collaborators and the critical voices of the patient community who were essential to this progress and continue to help advance our mission of seeking gene therapy cures. I look forward to building off the successes of 2022 and continuing our progress in 2023."

Key Pipeline and Operational Updates

•
Announced positive clinical data from Phase 1 trial of RP-A501 for Danon Disease. The Company provided an update at the 41st Annual J.P. Morgan Healthcare Conference that continued to demonstrate RP-A501 was generally well tolerated with evidence of restored expression of the deficient LAMP2 protein and durable improvement or stabilization of clinical parameters in the adult and pediatric Danon Disease patients treated in the Phase 1 study. The Company previously presented positive data from the study at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2022. The FDA recently granted Regenerative Medicine Advanced Therapy (RMAT) designation to RP-A501 that will provide the benefits of added intensive FDA guidance and expedited review through the program’s development. The initiation of the Phase 2 pivotal trial is on track for the second quarter of 2023. As previously disclosed, the Company anticipates pursuing a single arm, open-label trial with a biomarker-based composite endpoint and a natural history comparator.

•
Successfully completed two in-house AAV production runs at state-of-the-art, Current Good Manufacturing Practice (cGMP) manufacturing and R&D facility in Cranbury, N.J. In-house production runs of AAV drug product for the planned Phase 2 pivotal study in Danon Disease resulted in high-quality drug substance enabling an approximately threefold increase in the number of patients treatable per batch, a significantly improved full versus empty particle ratio, and promising product comparability data generated to date compared to the Phase 1 material manufactured externally.

•
Announced positive top-line data from Phase 2 pivotal trial of RP-L201 for Leukocyte Adhesion Deficiency-I (LAD-I). Positive top-line data presented at the 2022 Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) and at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting demonstrated 100% overall survival at 12 months post-infusion via Kaplan Meier estimate and a statistically significant reduction in all hospitalizations, infection- and inflammatory-related hospitalizations and prolonged hospitalizations for all nine LAD-I patients with three to 24 months of available follow-up. Data also showed evidence of resolution of LAD-I-related skin rash and restoration of wound repair capabilities. The Company recently presented data at the Tandem Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and Center for International Blood & Marrow Transplant Research (CIBMTR) in February 2023 demonstrating all patients sustained neutrophil CD18 restoration and expression of more than 10% (range: 15%-89%, median: 51%), as of the November 2, 2022, cut-off date. At the congress, the RP-L201 program received first place in the abstract awards competition. Based on the data from the Phase 2 pivotal LAD-I trial, Rocket anticipates submitting a Biologics License Application (BLA) in the second quarter of 2023.

•
Announced positive top-line data from Phase 2 pivotal trial of RP-L102 for Fanconi Anemia (FA). Data presented at the 64th ASH (Free ASH Whitepaper) Annual Meeting (cut-off October 26, 2022), indicated that RP-L102 demonstrated phenotypic correction in at least six of 10 evaluable patients with ≥12 months of follow-up as demonstrated by increased resistance to mitomycin-C (MMC) in bone marrow (BM)-derived colony forming cells, concomitant genetic correction and hematologic stabilization. A seventh patient has displayed evidence of progressively increasing genetic correction as demonstrated by peripheral blood and BM vector copy numbers (VCNs), with recent development of MMC resistance and indicators of hematologic stability after 36 months of follow-up. Data demonstrated increased resistance to MMC in five patients at least at two timepoints, ranging from 74% to 94% at the most recently evaluated timepoint. The safety profile of RP-L102 was highly favorable, and the treatment, administered without any cytotoxic conditioning, was well tolerated. The Company recently presented these data at the Tandem Meetings of ASTCT and CIBMTR in February 2023 and the RP-L102 program received second place in the abstract awards competition. Based on the data from the Phase 2 pivotal Fanconi Anemia trial, Rocket anticipates submitting a BLA in the fourth quarter of 2023.

•
Announced positive clinical data from Phase 1 trial of RP-L301 for Pyruvate Kinase Deficiency (PKD). Data presented at the 64th ASH (Free ASH Whitepaper) Annual Meeting (cut-off October 26, 2022) demonstrated that both patients at 24 months post-RP-L301 infusion had robust and sustained efficacy demonstrated by normalized hemoglobin (from baseline levels in the 7.0-7.5 g/dL range), improved hemolysis parameters, independence from red blood cell transfusions and improved quality of life both reported anecdotally and as documented via formal quality of life assessments. The safety profile appears highly favorable, with no RP-L301-related serious adverse events through 24 months post-infusion in both adult patients. Adult and pediatric enrollment is completed in the Phase 1 study. The company recently presented these data at the Tandem Meetings of ASTCT and CIBMTR in February 2023. Phase 2 pivotal trial initiation is anticipated in the fourth quarter of 2023.

•
Raised $197.7M to develop full pipeline of assets. During 2022, the Company completed a follow-on offering of common stock for net proceeds of $108.1 million, sold shares of common stock for net proceeds of $46.6 million pursuant to the at-the-market offering program and acquired cash and cash equivalents of $43.0 million as part of the acquisition of Renovacor.

•
Acquired Renovacor, extending leadership in AAV-based cardiac gene therapy. In December 2022, Rocket completed the acquisition of Renovacor, bringing in $43.0 million of non-dilutive capital. The acquisition also provided Rocket access to an AAV-based gene therapy targeting BAG3-associated dilated cardiomyopathy (DCM), a severe form of heart failure. Additionally, Rocket gained access to world-class scientific collaborators, a robust intellectual property portfolio and personnel with expertise in BAG3-DCM.

•
Strengthened Board of Directors and leadership team with new appointments. Broadened cardiovascular experience with the appointment of Fady Malik, M.D., Ph.D. to Rocket’s Board of Directors. Dr. Malik brings nearly 25 years of experience as an internationally recognized cardiovascular physician-scientist and highly successful biopharmaceutical executive. In addition, Rocket appointed Mayo Pujols as Executive Vice President, Chief Technical Officer. Mr. Pujols has nearly 30 years of experience in leadership roles across technical operations, quality operations, validation, process development and cGMP manufacturing. Rocket also appointed Carlos Martin as Senior Vice President, Chief Commercial Officer. Mr. Martin brings over 20 years of global commercial leadership gained at Novartis, Schering Plough and Eli Lilly.

•
Recognized Rare Disease Day with an event at NASDAQ Tower in New York City. On February 28, 2022, Rocket hosted its annual Rare Disease Day celebration highlighting the theme, "Rare, But Not Alone." More than 250 members of the global rare disease community and Rocket team gathered in person and virtually to hear about the impact of rare disease and clinical research from patients, families, advocacy groups and scientific collaborators and innovators – including Dr. Moris Danon, who first identified Danon Disease. The event concluded with the lighting of the Empire State Building, as well as other global landmarks, in Rare Disease Day colors.

Upcoming Investor Conferences

•
Cowen’s 43rd Annual Health Care Conference: March 6-8, 2023

•
Needham 21st Annual Virtual Healthcare Conference: April 17-20, 2023

Fourth Quarter and Full Year 2022 Financial Results

•
Cash position. Cash, cash equivalents and investments as of December 31, 2022, were $399.7 million.

•
R&D expenses. Research and development expenses were $50.0 million and $165.6 million for the three and twelve months ended December 31, 2022, compared to $32.2 million and $125.5 million for the three and twelve months ended December 31, 2021. The increase in R&D expenses was primarily driven by increases in manufacturing and development costs of $26.3 million, laboratory supplies of $6.6 million, compensation and benefits expense of $11.5 million due to increased R&D headcount and direct materials of $3.6 million. Increases noted were offset by a decrease in license fees of $12.9 million attributable to the expense in connection with warrants to purchase shares of common stock recorded for the year ended December 31, 2021.

•
G&A expenses. General and administrative expenses were $19.0 million and $58.8 million for the three and twelve months ended December 31, 2022, compared to $12.2 million and $41.8 million for the three and twelve months ended December 31, 2021. The increase in G&A expenses was primarily driven by increases in commercial preparation expenses which consists of commercial strategy, medical affairs, market development and pricing analysis of $4.9 million, compensation and benefits of $4.4 million due to increased G&A headcount and acquisition related expense of $3.2 million related to the Renovacor acquisition which closed on December 1, 2022.

•
Net loss. Net loss was $66.7 million and $221.9 million or $0.92 and $3.26 per share (basic and diluted) for the three and twelve months ended December 31, 2022, compared to $44.2 million and $169.1 million or $0.69 and $2.67 per share (basic and diluted) for the three and twelve months ended December 31, 2021.

•
Shares outstanding. 79,123,312 shares of common stock were outstanding as of December 31, 2022.

Financial Guidance

•
Cash position. As of December 31, 2022, Rocket had cash, cash equivalents and investments of $399.7 million. Rocket expects such resources will be sufficient to fund its operations through 2024, including producing AAV cGMP batches at the Company’s Cranbury, N.J. R&D and manufacturing facility and continued development of our six clinical and/or preclinical programs.

About Rocket Pharmaceuticals, Inc.
Rocket Pharmaceuticals, Inc. (NASDAQ: RCKT) is advancing an integrated and sustainable pipeline of investigational genetic therapies designed to correct the root cause of complex and rare disorders. The Company’s platform-agnostic approach enables it to design the best therapy for each indication, creating potentially transformative options for patients afflicted with rare genetic diseases. Rocket’s clinical programs using lentiviral vector (LV)-based gene therapy are for the treatment of Fanconi Anemia (FA), a difficult to treat genetic disease that leads to bone marrow failure and potentially cancer, Leukocyte Adhesion Deficiency-I (LAD-I), a severe pediatric genetic disorder that causes recurrent and life-threatening infections which are frequently fatal, and Pyruvate Kinase Deficiency (PKD), a rare, monogenic red blood cell disorder resulting in increased red cell destruction and mild to life-threatening anemia. Rocket’s first clinical program using adeno-associated virus (AAV)-based gene therapy is for Danon Disease, a devastating, pediatric heart failure condition. Rocket also has preclinical AAV-based gene therapy programs in PKP2-arrhythmogenic cardiomyopathy (ACM) and BAG3-associated dilated cardiomyopathy (DCM). For more information about Rocket, please visit www.rocketpharma.com.

Rocket Cautionary Statement Regarding Forward-Looking Statements
Various statements in this release concerning Rocket’s future expectations, plans and prospects, including without limitation, Rocket’s expectations regarding the safety and effectiveness of product candidates that Rocket is developing to treat Fanconi Anemia (FA), Leukocyte Adhesion Deficiency-I (LAD-I), Pyruvate Kinase Deficiency (PKD), Danon Disease (DD) and other diseases, the expected timing and data readouts of Rocket’s ongoing and planned clinical trials, the expected timing and outcome of Rocket’s regulatory interactions and planned submissions, Rocket’s plans for the advancement of its Danon Disease program, including its planned pivotal trial, and the safety, effectiveness and timing of related pre-clinical studies and clinical trials, may constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995 and other federal securities laws and are subject to substantial risks, uncertainties and assumptions. You should not place reliance on these forward-looking statements, which often include words such as "aim," "anticipate," "believe," "can," "continue," "design," "estimate," "expect," "intend," "may," "plan," "potential," "will give," "seek," "will," "may," "suggest" or similar terms, variations of such terms or the negative of those terms. Although Rocket believes that the expectations reflected in the forward-looking statements are reasonable, Rocket cannot guarantee such outcomes. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Rocket’s ability to monitor the impact of COVID-19 on its business operations and take steps to ensure the safety of patients, families and employees, the interest from patients and families for participation in each of Rocket’s ongoing trials, patient enrollment, trial timelines and data readouts, our expectations regarding our drug supply for our ongoing and anticipated trials, actions of regulatory agencies, which may affect the initiation, timing and progress of pre-clinical studies and clinical trials of its product candidates, our ability to submit regulatory filings with the U.S. Food and Drug Administration (FDA) and to obtain and maintain FDA or other regulatory authority approval of our product candidates, Rocket’s dependence on third parties for development, manufacture, marketing, sales and distribution of product candidates, the outcome of litigation, our competitors’ activities, including decisions as to the timing of competing product launches, pricing and discounting, our integration of an acquired business, which involves a number of risks, including the possibility that the integration process could result in the loss of key employees, the disruption of our ongoing business, or inconsistencies in standards, controls, procedures, or policies, our ability to successfully develop and commercialize any technology that we may in-license or products we may acquire and any unexpected expenditures, as well as those risks more fully discussed in the section entitled "Risk Factors" in Rocket’s Annual Report on Form 10-K for the year ended December 31, 2021, filed February 28, 2022 with the SEC and subsequent filings with the SEC including our Quarterly Reports on Form 10-Q. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and Rocket undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.

Three Months Ended December 31,

Twelve Months Ended December 31,

2022

2021

2022

2021

Operating expenses:

Research and development

$
50,037

$
32,161

$
165,570

$
125,476

General and administrative

19,044

12,171

58,773

41,772

Total operating expenses

69,081

44,332

224,343

167,248

Loss from operations

(69,081
)

(44,332
)

(224,343
)

(167,248
)
Research and development incentives

500

500

500

1,000

Interest expense

(467
)

(463
)

(1,862
)

(2,977
)
Interest and other income, net

1,245

849

3,889

3,068

Amortization of premium on investments – net

1,081

(801
)

(47
)

(2,912
)
Total other income (expense), net

2,359

85

2,480

(1,821
)
Net loss

$
(66,722
)

$
(44,247
)

$
(221,863
)

$
(169,069
)
Net loss per share attributable to common stockholders – basic and diluted

$
(0.92
)

$
(0.69
)

$
(3.26
)

$
(2.67
)
Weighted-average common shares outstanding – basic and diluted

72,889,548

64,470,930

68,148,925

63,235,417

December 31,

December 31,

2022

2021

Cash, cash equivalents, and investments

$
399,670

$
388,740

Total assets

551,807

497,020

Total liabilities

62,121

42,296

Total stockholders’ equity

489,686

454,724

On February 27, 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 and year ended December 31, 2022, and provided an update on corporate progress (Press release, Revolution Medicines, FEB 27, 2023, View Source [SID1234627741]).

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"2022 saw the entry of our first two RAS(ON) Inhibitor candidates, RMC-6236 (RASMULTI) and RMC-6291 (KRASG12C), into clinical development," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "For RMC-6236, initial pharmacokinetics, molecular, radiographic and tolerability/safety data provide encouraging evidence that we are dosing patients at clinically active and tolerated doses. Consistent with its preclinical profile, RMC-6236 has shown promising preliminary antitumor activity against multiple tumor types and genotypes. Combined with initial evidence of clinical activity for RMC-6291, we are encouraged that these data should have positive readthrough to our broad portfolio of RAS(ON) Inhibitors.

"In addition, IND-enabling development of RMC-9805, a mutant-selective RAS(ON) Inhibitor drug candidate designed to target cancers driven by the KRASG12D mutation, is progressing toward first-in-human dosing mid-year. And we recently announced the advancement of RMC-0708, a mutant-selective inhibitor of the KRASQ61H cancer variant, into IND-enabling development.

"As a result of the exceptional work of our entire organization, Revolution Medicines’ portfolio now includes clinical and development-stage assets that may be applicable to the majority of RAS-addicted cancers, including compounds targeting every major RAS cancer mutation hotspot — G12, G13 and Q61. Early results from our first wave of RAS(ON) Inhibitors support continued investment in advancing our development pipeline of clinical and preclinical RAS(ON) Inhibitors and clinical RAS Companion Inhibitors. Building on this ongoing portfolio progress and encouraging signs, part of management’s bandwidth is now directed toward defining the paths and steps we need to take now and over the next several years to ensure that we can maximize the value of these product candidates."

Clinical and Development Highlights

RAS(ON) Inhibitors

RMC-6236 (RASMULTI)
RMC-6236 is an oral RAS(ON) Inhibitor designed to treat patients with cancers driven by a variety of RAS mutations, including KRASG12D, KRASG12V and KRASG12R. Initially being evaluated as monotherapy, it may also be deployed as a RAS Companion Inhibitor in combination with mutant-selective RAS(ON) Inhibitors.

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 KRASG12D, KRASG12V and KRASG12R.

Early findings have shown that RMC-6236 is orally bioavailable in patients, exhibiting pharmacokinetics consistent with our preclinical data and delivering dose-dependent increases in plasma exposure on once daily dosing and is generally well tolerated. A recommended phase 2 dose has not been established yet.

36 patients were evaluable for initial safety and tolerability in the study as of the data cut-off date of February 17, 2023. All of these patients had been previously treated with standard of care and/or other regimens, with an overall median of three prior treatments. As of this data cut-off, RMC-6236 was generally well tolerated in this group. Some patients have exhibited predicted and manageable on-target normal tissue effects.

12 patients — three non-small cell lung cancer (NSCLC) and nine pancreatic cancer —treated with RMC-6236 at doses of 40 mg, 80 mg or 120 mg daily were efficacy evaluable as of the February 17, 2023 data cut-off date. All 12 patients exhibited stable disease or better as their best response; 10 of these had reductions in tumor volume as of the data cut-off date. Importantly, as of the data cut-off date, all patients remained on study, with total duration of approximately 1.5-4.5 months. One patient with KRASG12D NSCLC treated with 80 mg achieved a partial response (PR) on first re-staging scan that was subsequently confirmed by a follow-up scan. One patient with metastatic KRASG12D pancreatic cancer who progressed following a third course of chemotherapy received RMC-6236 80 mg daily and has tolerated it well. At baseline the patient had three distinct lesions in the lung that are followed radiographically. At six weeks, all three tumor lesions were reduced in size, reported as 17% reduction by Response Evaluation Criteria in Solid Tumors (RECIST). At 12 weeks, all three residual lesions were barely detectable, and the patient achieved a 70% reduction and PR by RECIST. The patient continues on study as of the data cut-off date and confirmation of the response awaits a follow-up scan.
The company currently plans to provide further evidence of first-in-class single agent activity for RMC-6236 in mid-2023.
RMC-6291 (KRASG12C)
RMC-6291, an oral, selective, covalent inhibitor of KRASG12C(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 publicly reported inhibitor of KRASG12C that exhibits a highly differentiated mechanism of action.

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. Early findings have shown that RMC-6291 is orally bioavailable and has exhibited pharmacokinetics consistent with preclinical findings and is generally well tolerated. A recommended phase 2 dose and schedule have not been established yet. Initial molecular and radiographic data indicate that the company is dosing RMC-6291 in a pharmacologically active range.

The company currently plans to provide preliminary evidence of a superior profile for this compound in the second half of 2023.
RMC-9805 (KRASG12D)
RMC-9805 is an oral, selective, covalent inhibitor of KRASG12D(ON), the most common driver of RAS-addicted human cancers, predominantly among patients with pancreatic cancer, NSCLC or colorectal cancer (CRC). The company believes RMC-9805 is the first oral and covalent inhibitor of KRASG12D.

The company currently expects to announce dosing of the first patient in a monotherapy dose-escalation study of RMC-9805 in mid-2023.
RAS Innovation Engine
Beyond this first wave of RAS(ON) Inhibitors, the company continues expanding its pipeline of RAS(ON) Inhibitor candidates.

RMC-0708 is a potent, oral and selective non-covalent inhibitor of the KRASQ61H(ON) cancer variant. KRASQ61H is found in approximately 10,000 new cancer cases in the U.S. each year divided evenly across lung cancer, CRC, pancreatic cancers and multiple myeloma. RMC-0708 is the company’s first mutant-selective RAS(ON) inhibitor drug candidate to engage its RAS target non-covalently.

RMC-8839 is a potent, oral and selective 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 continues drug discovery efforts in RAS(ON) Inhibitor pipeline expansion programs focused on RAS mutation hotspots including KRASG12R, KRASG12V, KRASG13D, RASQ61X and other important targets.
RAS Companion Inhibitors

RMC-4630 (SHP2)
RMC-4630 is a clinical-stage, oral inhibitor of SHP2, which contributes to tumor survival and growth in many RAS-addicted cancers.

RMC-4630 and KRASG12C Inhibitor Lumakras (sotorasib)

CodeBreaK 101c: Amgen has reported preliminary results from this Phase 1b trial evaluating the combination of RMC-4630 with the KRASG12C inhibitor sotorasib in patients with advanced KRASG12C-mutated solid tumors. The results demonstrated that the combination was safe and tolerable, and showed promising early clinical activity in NSCLC patients with KRASG12C mutations, particularly in patients who were KRASG12C inhibitor-naïve.

RMC-4630-03: Revolution Medicines continues conducting its global Phase 2 trial RMC-4630-03 (NCT05054725), a multicenter, open-label study of RMC-4630 in combination with sotorasib for patients with NSCLC with a KRASG12C mutation who have failed prior standard therapy and who have not previously been treated with a KRASG12C inhibitor. The company is conducting the trial in collaboration with Amgen, which is supplying sotorasib to trial sites globally. The study is fully enrolled and Revolution Medicines currently expects to provide topline data from this study in the second half of 2023.

The company expects to evaluate RMC-4630 in combination with its RAS(ON) Inhibitors in the future.
Sanofi, Revolution Medicines’ partner for the development of RMC-4630, provided notice of termination of their global SHP2 development and commercialization collaboration, effective as of June 2023. The companies are collaborating for the transition of all Sanofi’s rights and obligations related to RMC-4630 back to Revolution Medicines over the first half of 2023. Following termination, Revolution Medicines will regain all global rights to RMC-4630.

RMC-5552 (mTORC1/4EPB1)
RMC-5552 is a first-in-class, bi-steric mTORC1-selective inhibitor designed to suppress phosphorylation and inactivation of 4EBP1 in cancers with hyperactive mTORC1 signaling, including certain RAS-addicted cancers. The company aims to combine RMC-5552 with RAS(ON) Inhibitors in patients with cancers harboring RAS/mTOR pathway co-mutations.

Dose optimization continues in the company’s ongoing multicenter, open-label, Phase 1/1b dose-escalation study evaluating RMC-5552 monotherapy in patients with refractory solid tumors (NCT04774952). As with RMC-4630, the company expects to evaluate RMC-5552 in combination with its RAS(ON) Inhibitors in the future.

The company currently anticipates disclosing additional evidence of single agent activity for this compound in 2023.
Fourth Quarter and Full Year 2022 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $644.9 million as of December 31, 2022, compared to $577.1 million as of December 31, 2021. The increase was primarily attributable to the company’s public equity offering in July 2022.

Revenue: Total revenue was $15.3 million for the quarter ended December 31, 2022, compared to $9.5 million for the quarter ended December 31, 2021 and consisted of revenue from the company’s collaboration agreement on SHP2 inhibitors with Sanofi. During the quarter ended December 31, 2022, the company recorded a non-cash GAAP accounting adjustment that increased collaboration revenue by $7.6 million. This non-cash revenue adjustment was due to the termination of the Sanofi collaboration agreement which resulted in changes to the company’s estimates of the accounting transaction price and estimated percentage of completion of work performed to date and resulted in a cumulative catch-up adjustment to collaboration revenue in the quarter.

Total revenue was $35.4 million for the year ended December 31, 2022, compared to $29.4 million for the year ended December 31, 2021. The increase in revenue was primarily due to the non-cash revenue adjustment.

R&D Expenses: Research and development expenses were $66.1 million for the quarter ended December 31, 2022, compared to $53.7 million for the quarter ended December 31, 2021. Research and development expenses were $253.1 million for the year ended December 31, 2022, compared to $186.9 million for the year ended December 31, 2021. The increases were primarily due to an increase in RMC-6236 and RMC-6291 expenses as a result of commencing clinical trials in 2022, an increase in personnel-related expenses related to additional headcount, an increase in research expenses associated with the company’s pre-clinical research portfolio, and an increase in stock-based compensation.

G&A Expenses: General and administrative expenses were $10.9 million for the quarter ended December 31, 2022, compared to $8.7 million for the quarter ended December 31, 2021. General and administrative expenses were $40.6 million for the year ended December 31, 2022, compared to $30.5 million for the year ended December 31, 2021. The increases were 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 $56.5 million for the quarter ended December 31, 2022, compared to net loss of $52.7 million for the quarter ended December 31, 2021. Net loss was $248.7 million for the year ended December 31, 2022, compared to net loss of $187.1 million for the year ended December 31, 2021.

Financial Guidance

Revolution Medicines expects full year 2023 GAAP net loss to be between $335 and $365 million, which includes estimated non-cash stock-based compensation expense of $40 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 through 2024.

Webcast
Revolution Medicines will host a webcast this afternoon, February 27, 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 FEBRUARY 27, 2023 Recursion (Nasdaq : RXRX), a clinical stage TechBio company leading the space by decoding biology to industrialize drug discovery, reported business updates and financial results for its fourth quarter and fiscal year ended December 31, 2022 (Press release, Recursion Pharmaceuticals, FEB 27, 2023, View Source [SID1234627740]).

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"2022 was a fantastic year for Recursion where we continued to deliver on the promise of our pipeline with five clinical trial initiations, continued execution of our Bayer and Roche-Genentech partnerships, and continued to grow our proprietary data moat through our scale and accelerating capabilities across transcriptomics, digital in vivo tolerability, and chemistry," said Chris Gibson, Ph.D., Co-Founder & CEO at Recursion. "I believe that the work we have done in 2022 is setting the stage for significant value-creation in the coming 12-24 months. What is most exciting to me is the rapid uptick in the world’s curiosity around ML and AI due to advances in other industries. I think it is important to reflect on the tremendous advancements taking place around us and I believe we are best positioned to deploy similar tools across the drug discovery and development process."

Summary of Business Highlights

•Internal Pipeline
◦Cerebral Cavernous Malformation (CCM) (REC-994): Our Phase 2 SYCAMORE clinical trial is a double-blind, placebo-controlled safety, tolerability and exploratory efficacy study of this drug candidate in 60 participants with CCM. At this time, we continue to actively enroll participants. We expect to share top-line data in 2H 2024.
◦Neurofibromatosis Type 2 (NF2) (REC-2282): Our Phase 2/3 POPLAR clinical trial is a parallel group, two stage, randomized, multicenter study of this drug candidate in approximately 90 participants with progressive NF2-mutated meningiomas. At this time, we continue to actively enroll participants. We expect to share a Phase 2 interim safety analysis in 2024.
◦Familial Adenomatous Polyposis (FAP) (REC-4881): Our Phase 2 TUPELO clinical trial is a multicenter, randomized, double-blind, placebo-controlled two-part clinical trial to evaluate efficacy, safety, and pharmacokinetics of this drug candidate in patients with FAP. Recent protocol amendments are aimed at accelerating the quality and pace of the trial.
◦AXIN1 or APC Mutant Cancers (REC-4881): In October 2022, we announced the nomination of REC-4881 for the potential treatment of AXIN1 or APC mutant cancers with an initial focus on hepatocellular carcinoma and ovarian cancer. We

expect to initiate a Phase 1b/2 biomarker enriched basket study across select AXIN1 or APC mutant tumors in early 2024.
◦Clostridioides difficile Colitis (REC-3964): Our Phase 1 clinical trial is a first-in-human protocol evaluating single and multiple doses of REC-3964 in healthy volunteers and will assess the safety, tolerability and pharmacokinetic profile of REC-3964. At this time, we continue to actively enroll participants. We expect to share safety and PK data in 2H 2023.
◦HR-Proficient Ovarian Cancer: In January 2023, we disclosed that RBM39 (previously identified as Target Gamma) is the novel CDK12-adjacent target identified by the Recursion OS. We believe that modulating RBM39 could lead to a potential treatment of HR-proficient ovarian cancer. We expect this program to reach IND-enabling studies in 2023.
◦Enhancing Anti-PD-(L)1 Response by Inhibiting Novel Targets (Target Alpha): This program is a potential first-in-class novel chemical entity with a novel polypharmacologic mechanism of action for which we have not yet disclosed the targets. We expect this program to reach IND-enabling studies in 2023.
•Transformational Collaborations
We continue to advance efforts to discover potential new therapeutics with our strategic partners in the areas of fibrotic disease (Bayer) as well as neuroscience and a single indication in gastrointestinal oncology (Roche-Genentech). In the near-term, there is the potential for option exercises associated with partnership programs, option exercises associated with map building initiatives or data sharing and additional partnerships in large, intractable areas of biology or technological innovation.
•Recursion OS
◦Cell and Tissue Culturing: In 2022, we industrialized stem cell production and produced over 500 billion hiPSC-derived cells in-house to enable neurology research. We believe that this volume of biological material could make Recursion one of the largest producers of neural hiPSC-derived cells in the world and could give Recursion flexibility around its consumables and collaboration activities.
◦Chemical Technology: We have begun configuring our automated drug metabolism and pharmacokinetics (DMPK) wet-lab module into the Recursion OS. Once fully onboarded, this module will enable scaled, automated processing and evaluation of compounds for plasma protein binding, microsomal stability, and cell permeability. With an operational capacity of up to 500 compounds per week, this module lays the foundation for us to generate additional proprietary data moats that enable the training of ML and AI algorithms.
◦Publicly Available Dataset and Application: In January 2023, Recursion released RxRx3, its largest open-source cellular imaging dataset to date, as well as MolRec, an interactive application to explore compound and gene relationships. Both of these offerings are free to the public and can be found at www.rxrx.ai.
•Additional Corporate Updates
◦Letter to Shareholders: Recursion Co-Founder & CEO Chris Gibson, Ph.D. wrote an annual letter to shareholders which may be found in the 10-K report filed with the SEC, ahead of Part I.

◦Download Day: In January 2023, Recursion hosted Download Day, a R&D-focused event highlighting aspects of Recursion’s platform, data, programs, partnerships and culture. Materials from this event can be found at www.Recursion.com/download-day.
◦Facilities: Recursion completed an expansion of its headquarters in Salt Lake City, making room for research and development activities related to expanding our human tissue culture and chemical compound handling capabilities, enabling new biological contexts for map building and scaling sequencing and automated DMPK assays.
◦ESG Reporting: In October 2022, Sustainalytics ranked Recursion in the top 100 of pharmaceutical companies with respect to its ESG efforts (approximately top 10%). In March 2023, Recursion plans to release an updated ESG report.
◦Annual Shareholder Meeting: The Recursion Annual Shareholder Meeting will be held on June 16, 2023 at 12:00 pm Mountain Time.

Fourth Quarter and Fiscal Year 2022 Financial Results

•Cash Position: Cash, cash equivalents and investments were $549.9 million as of December 31, 2022, compared to $516.6 million as of December 31, 2021.
•Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $13.7 million for the fourth quarter of 2022, compared to $2.5 million for the fourth quarter of 2021. Total revenue, consisting primarily of revenue from collaboration agreements, was $39.8 million for the year ended December 31, 2022, compared to $10.2 million for the year ended December 31, 2021. The increase in both periods in 2022 was due to revenue recognized from our Roche-Genentech collaboration.
•Research and Development Expenses: Research and development expenses were $44.0 million for the fourth quarter of 2022, compared to $48.3 million for the fourth quarter of 2021. Research and development expenses were $155.7 million for the year ended December 31, 2022, compared to $135.3 million for the year ended December 31, 2021. The increase in 2022 research and development expenses compared to the prior year was due to increased clinical costs as studies progressed.
•General and Administrative Expenses: General and administrative expenses were $19.8 million for the fourth quarter of 2022, compared to $19.2 million for the fourth quarter of 2021. General and administrative expenses were $81.6 million for the year ended December 31, 2022, compared to $57.7 million for the year ended December 31, 2021. The increase in 2022 general and administrative expenses compared to the prior year was due to the growth in size of the company’s operations, including an increase in salaries and wages of $14.3 million, a fixed asset write-down of $2.8 million, increased rent expense of $2.4 million and increases in other administrative costs associated with operating a growing company.
•Net Loss: Net loss was $57.5 million for the fourth quarter of 2022, compared to a net loss of $64.9 million for the fourth quarter of 2021. Net loss was $239.5 million for the year ended December 31, 2022, compared to a net loss of $186.5 million for the year ended December 31, 2021.

On february 27, 2023 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported it has entered into a securities purchase agreement with a single, healthcare-focused institutional investor for the purchase and sale of 3,809,524 shares of its common stock together with warrants to purchase up to 3,809,524 shares of common stock at a combined purchase price of $1.05 per share and accompanying warrant, pursuant to a registered direct offering (Press release, Genprex, FEB 27, 2023, View Source [SID1234627738]). The warrants will have an exercise price of $1.10, will be exercisable immediately and will expire five years from the date of issuance.

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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

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The closing of the offering is expected to occur on or about March 1, 2023, subject to the satisfaction of customary closing conditions. The gross proceeds from the offering are expected to be approximately $4 million, before deducting placement agent fees and other estimated offering expenses. The Company intends to use the net proceeds from the offering for general working capital purposes.

A.G.P./Alliance Global Partners is acting as sole placement agent for the offering.

This offering is being made pursuant to an effective shelf registration statement on Form S-3 (File No 333-239134) previously filed with the U.S. Securities and Exchange Commission (the "SEC"). A prospectus supplement describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected].

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 state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On February 27, 2023 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported that management will participate in two upcoming investor conferences (Press release, Arvinas, FEB 27, 2023, View Source [SID1234627737])

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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

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Cowen 43rd Annual Health Care Conference on Monday, March 6. Ron Peck, M.D., Chief Medical Officer, and Randy Teel, Ph.D., Senior Vice President, Corporate and Business Development, will participate in a fireside chat. A live audio webcast of the presentation will be available here and on the Events + Presentations section of the Company’s website.

Oppenheimer 33rd Annual Healthcare Conference on Monday, March 13. Ron Peck, M.D., Chief Medical Officer, and Randy Teel, Ph.D., Senior Vice President, Corporate and Business Development, will participate in a fireside chat. A live audio webcast of the presentation will be available here and on the Events + Presentations section of the Company’s website.