On November 8, 2022 IDEAYA Biosciences, Inc. (Nasdaq:IDYA), a synthetic lethality focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported financial results for the third quarter ended September 30, 2022 (Press release, Ideaya Biosciences, NOV 8, 2022, View Source [SID1234623422]).

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"Our clinical portfolio is maturing, with four potential first-in-class clinical-stage programs anticipated in the first half of 2023 – darovasertib (PKC), IDE397 (MAT2A), IDE161 (PARG) and our Pol Theta Helicase inhibitor development candidate. This broad pipeline of precision medicine therapeutics reflects our commitment to develop transformative therapies with the potential to improve patient lives," said Yujiro S. Hata, President and Chief Executive Officer, IDEAYA Biosciences. "We have built a unique platform in synthetic lethality and an organization with the capabilities to effectively discover and advance our growing preclinical and clinical precision medicine oncology pipeline. Importantly, we own or control all development and commercial rights and interests in our three most advanced programs," continued Mr. Hata.

IDEAYA’s most advance clinical program is darovasertib, a potential first-in-class small molecule oral protein kinase C (PKC) inhibitor for patients having tumors with GNAQ/11 mutations. The company reported positive Phase 2 interim clinical data for darovasertib and crizotinib synthetic lethal combination in metastatic uveal melanoma (MUM) in September 2022 and is targeting initiation of a potential registrational trial in MUM in the first quarter of 2023. IDEAYA also reported preliminary clinical proof-of-concept for a potential expansion opportunity in (neo)adjuvant uveal melanoma (UM) and is targeting initiation of company-sponsored trial for darovasertib monotherapy in neoadjuvant UM in the fourth quarter of 2022.

IDEAYA’s clinical pipeline also includes IDE397, a potential first-in-class Phase 2 MAT2A inhibitor, for patients having tumors with MTAP deletion, which represents approximately 15% of all solid tumors. Clinical data from Phase 1 monotherapy dose escalation reflects robust target engagement and an observed therapeutic window, positioning IDE397 to evaluate clinical efficacy – as monotherapy and multiple combination therapies. IDEAYA’s clinical development plan includes an emphasis on combination strategies, based on observed in vivo efficacy in preclinical studies. The company believes that IDE397 combination therapies could potentially enhance clinical efficacy in patients having tumors with MTAP deletion.

The company’s preclinical pipeline includes several potential first-in-class synthetic lethal therapeutics advancing toward the clinic. IDEAYA is targeting an IND in the fourth quarter of 2022 for IDE161, its PARG inhibitor, for patients having tumors with HRD. In collaboration with GSK, the company is targeting first-in-human clinical evaluation in the first half of 2023 for its Pol Theta Helicase inhibitor development candidate in combination with niraparib for patients having tumors with HRD. Its Werner Helicase program continues in collaboration with GSK toward development candidate nomination in 2023.

Program Updates
Key highlights for IDEAYA’s pipeline programs include:

Darovasertib (PKC)
IDEAYA continues to advance its Phase 1/2 clinical trial evaluating darovasertib (IDE196), a potent and selective PKC inhibitor, in combination with crizotinib, a cMET inhibitor, in metastatic uveal melanoma (MUM). The company is also clinically evaluating darovasertib in (neo)adjuvant uveal melanoma (UM) as monotherapy through an investigator sponsor clinical trial (IST).

IDEAYA is planning to initiate a company-sponsored clinical trial to evaluate darovasertib in (neo)adjuvant uveal melanoma. The company is also evaluating other potential darovasertib expansion opportunities, including in cMET driven tumors and in KRAS-mutation tumors.

Darovasertib / Crizotinib Combination Therapy in Metastatic Uveal Melanoma (MUM)
IDEAYA is continuing patient enrollment into the darovasertib / crizotinib combination arm of the Phase 1/2 clinical trial in MUM under clinical trial collaboration and supply agreements with Pfizer, with continued emphasis on enrollment of first-line MUM patients. Highlights:

IDEAYA presented interim Phase 2 darovasertib and crizotinib clinical combination data in September 2022. The reported data, based on an unlocked database with a data analyses cutoff date of June 26, 2022, showed robust clinical activity. These investigator-reviewed data by RECIST 1.1 include, as of the data analysis cutoff date:
89% of patients show tumor shrinkage in Any-Line MUM: 31 of 35 evaluable patients showed tumor shrinkage as determined by target lesion size reduction;
83% Disease Control Rate (DCR) in Any-Line MUM: 29 of 35 evaluable patients showed stable disease or better as determined by target lesion size reduction;
50% Overall Response Rate (ORR) in First-Line MUM: 4 of 8 evaluable patients had a confirmed partial response;
31% Overall Response Rate (ORR) in Any-Line MUM: 11 of 35 evaluable patients had a confirmed partial response;
43% of patients with >30% Tumor Reduction in Any-Line MUM: 15 of 35 evaluable patients observed partial responses with >30% tumor reduction, including 11 confirmed and 4 unconfirmed partial responses;
Median Study Follow-Up of 6.5 months for First-Line MUM patients and 7.8 months for Any-Line MUM patients;
Median Duration of Response (DOR) in evaluable First-Line MUM patients has not yet been reached and 4 of 4 patients with confirmed PR’s in First-Line MUM remain in response; median DOR in evaluable Any-Line MUM patients has not yet been reached and 7 of 11 patients with confirmed PR’s in Any-Line MUM remain in response;
Median Progression Free Survival (PFS) in First-Line MUM patients has not yet been reached and is >5 months in evaluable First-Line MUM patients; median PFS for evaluable Any-Line MUM patients is ~5 months; and
The darovasertib and crizotinib combination therapy has indicated a manageable adverse event profile in MUM patients (n=37) at the combination expansion doses, with a low rate of drug-related serious adverse events (SAEs) and with no Grade 4 or Grade 5 drug-related adverse events observed as of the data analysis cutoff date of June 26, 2022;
Targeting initiation of a potential registration-enabling trial for the darovasertib and crizotinib combination in MUM in Q1 2023, subject to FDA feedback and guidance, in collaboration with Pfizer under a clinical collaboration and supply agreement
In April 2022, the U.S. FDA designated darovasertib as an Orphan Drug in Uveal Melanoma, including MUM
Darovasertib – (Neo)Adjuvant Uveal Melanoma (UM)
IDEAYA is evaluating the potential for darovasertib in neoadjuvant and/or adjuvant uveal melanoma. Highlights:

(Neo)adjuvant UM represents a significant expansion opportunity – with a potential annual incidence of approximately 8,700 patients aggregate in US and Europe
Initiated an Investigator Sponsored Trial in coordination with St. Vincent’s Hospital Sydney Limited to evaluate darovasertib monotherapy in (neo)adjuvant UM patients
Reported preliminary clinical proof-of-concept data in September 2022, with observed clinical activity supporting potential darovasertib use in the (neo)adjuvant uveal melanoma setting. As of a data cut-off date of August 19, 2022, these data include observed tumor shrinkage by investigator review of primary ocular lesions in 5 of 5 (100%) UM or MUM patients treated as monotherapy or in combination with crizotinib and observed improvement in visual symptoms in the affected eye in two MUM patients having intact primary tumors
Targeting initiation of an IDEAYA-sponsored clinical trial in Q4 2022 to further evaluate darovasertib monotherapy in neoadjuvant UM patients, including potential clinical endpoints such as vision and organ preservation which would be temporally proximal to primary interventional treatments
Darovasertib – Other Potential Indications
IDEAYA is evaluating the potential for darovasertib in other oncology indications, including in cMET-driven tumors and RAS-mutation tumors. Highlights:

Evaluating darovasertib in combination with crizotinib, an investigational cMET inhibitor, in preclinical studies in cMET-driven tumors, such as NSCLC or HCC. Subject to preclinical evaluation and portfolio priorities, we may evaluate this combination in a Phase 1/2 clinical trial in collaboration with Pfizer under a clinical collaboration and supply agreement
Evaluating darovasertib in combination with a KRAS inhibitor in preclinical studies in KRAS-driven solid tumors
IDE397 (MAT2A)
IDEAYA is clinically evaluating IDE397, a potent and selective small molecule inhibitor targeting methionine adenosyltransferase 2a (MAT2A), in patients having solid tumors with methylthioadenosine phosphorylase (MTAP) deletion, a patient population estimated to represent approximately 15% of solid tumors. IDEAYA is continuing clinical development of IDE397 in its Phase 1/2 clinical trial, IDE397-001 (NCT04794699). Highlights:

Patients are being identified by next generation sequencing (NGS) or by MTAP immunohistochemistry (IHC) assay with confirmatory NGS
Initiated and actively enrolling patients into monotherapy expansion cohorts, with a focus on squamous cell NSCLC and esophagogastric cancer, consistent with preclinical efficacy and translational data
Initiated combination dose escalation cohorts with enrollment open for combinations of IDE397 with pemetrexed and taxanes, each of which are standard-of-care agents used as early-line therapies in NSCLC, mesothelioma and other solid tumor indications. The combination of IDE397 with pemetrexed is a novel and potential first-in-class combination of a MAT2A inhibitor with an antifolate agent.
Entered into Clinical Trial Collaboration and Supply Agreement with Amgen to clinically evaluate IDE397 MAT2A inhibitor in combination with AMG 193, Amgen’s investigational small molecule MTA-cooperative inhibitor of PRMT5, in MTAP-null solid tumors. The combination of IDE397 with AMG 193 is a novel and potential first-in-class synthetic lethality combination which targets two distinct and mechanistically complementary nodes of the MTAP methylation pathway – MAT2A and PRMT5, providing a complementary approach for targeting MTAP-deletion tumors.
IDEAYA owns all right, title and interest in and to IDE397 and the MAT2A program, including all worldwide commercial rights thereto, following GSK waiver in August 2022 of its right to exercise its option to obtain an exclusive license to further develop and commercialize IDE397, as well as other IDEAYA compounds, if any, directly targeting MAT2A
Demonstrated IDE397 clinical tumor pharmacodynamic modulation based on ctDNA Molecular Responses observed in thirteen evaluable patients with liquid biopsy samples available at baseline and after first treatment cycle, including:
31% (n=4 of 13) of evaluable patients treated with IDE397 across all dose escalation Cohorts 1 thru 6 observed ctDNA molecular responses
75% (n=3 of 5) of evaluable patients treated with IDE397 at higher doses in Cohorts 5 and 6 observed ctDNA molecular responses
100% (n=2 of 2) of evaluable NSCLC patients observed ctDNA molecular responses
PARG
IDEAYA is advancing its poly (ADP-ribose) glycohydrolase (PARG) inhibitor development candidate, IDE161, in patients having tumors with a defined biomarker based on genetic mutations and/or molecular signature. IDE161 is a potential first-in-class PARG inhibitor development candidate for patients having tumors with homologous recombination deficiencies (HRD), including BRCA1 and BRCA2, and potentially other alterations, in solid tumors such as breast cancer or ovarian cancer. PARG is a novel target in the same clinically validated biological pathway as poly (ADP-ribose) polymerase (PARP). IDEAYA owns or controls all commercial rights in its PARG program. Highlights:

Targeting IND for IDE161 in the fourth quarter of 2022
Considering potential development approaches based on observed activity of IDE161 in PARPi resistant and/or platinum-resistant tumors, differentiated sensitivity relative to PARP inhibitors, and improved preliminary safety profile relative to PARP inhibitors
Pol Theta
IDEAYA’s DNA Polymerase Theta, (Pol Theta) program targets tumors with BRCA or other homologous recombination (HR) mutations or homologous recombination deficiency (HRD). IDEAYA and GSK are collaborating on ongoing preclinical research and GSK will lead clinical development for the Pol Theta program. Highlights:

Selected a potential first-in-class Pol Theta Helicase inhibitor development candidate (DC) in collaboration with GSK
Observed tumor regressions in preclinical combination studies of Pol Theta Helicase DC with niraparib in multiple in vivo PDX and CDX HRD models
Targeting first-in-human clinical evaluation of Pol Theta Helicase inhibitor DC combination with niraparib in H1 2023 for patients having tumors with HRD
IDEAYA achieved the first preclinical development milestone in connection with ongoing IND-enabling studies to support evaluation of Pol Theta Helicase Inhibitor DC
IDEAYA is eligible to receive total development and regulatory milestones of up to $485 million aggregate from GSK, with up to $20 million in aggregate for advancing a Pol Theta Helicase inhibitor from preclinical to early Phase 1 clinical, including up to $10 million aggregate through IND effectiveness
Werner Helicase
IDEAYA is advancing preclinical research for an inhibitor targeting Werner Helicase for tumors with high microsatellite instability (MSI). IDEAYA and GSK are collaborating on ongoing preclinical research, and GSK will lead clinical development for the Werner Helicase program. Highlights:

Targeting selection of a Werner Helicase development candidate in 2023
IDEAYA is eligible to receive future development and regulatory milestones of up to $485 million aggregate from GSK, with potential for up to $20 million in aggregate for advancing a Werner Helicase inhibitor from preclinical to early Phase 1 clinical
Other Synthetic Lethality Pipeline Programs
IDEAYA is advancing additional preclinical research programs to identify small molecule inhibitors for an MTAP-synthetic lethality target, as well as for multiple potential first-in-class synthetic lethality programs for patients with solid tumors characterized by proprietary biomarkers or gene signatures.

General
IDEAYA continues to monitor Covid-19 and its potential impact on clinical trials and timing of clinical data results. Initiation of clinical trial sites, patient enrollment and ongoing monitoring of enrolled patients, including obtaining patient computed tomography (CT) scans, may be impacted for IDEAYA clinical trials evaluating IDE397 and darovasertib; the specific impacts are currently uncertain.

Corporate Updates
IDEAYA’s net income was $1.6 million for the three months ended September 30, 2022 and its net loss was $22.1 million for the three months ended June 30, 2022. As of September 30, 2022, the company had an accumulated deficit of $211.2 million.

As of September 30, 2022, IDEAYA had cash, cash equivalents and marketable securities of $393.9 million. IDEAYA believes that its cash, cash equivalents and marketable securities will be sufficient to fund its planned operations into 2026. These funds will support the company’s efforts through potential achievement of multiple preclinical and clinical milestones across multiple programs.

Our updated corporate presentation is available on our website, at our Investor Relations page: View Source

Financial Results
As of September 30, 2022, IDEAYA had cash, cash equivalents and short-term marketable securities totaling $393.9 million. This compared to cash, cash equivalents and short-term and long-term marketable securities of $323.8 million at June 30, 2022. The increase was attributable to receipt of aggregate net proceeds of $86.1 million from the sale of shares of IDEAYA common stock in an underwritten public financing in September 2022 and net proceeds of $8.9 million from the sale of shares of IDEAYA common stock under an at-the-market offering program during the three months ended September 30, 2022, partially offset by cash used in operations.

Collaboration revenue for the three months ended September 30, 2022 totaled $29.7 million compared to $5.9 million for the three months ended June 30, 2022. Collaboration revenue was recognized for the performance obligations satisfied through September 30, 2022 under the GSK Collaboration Agreement. The increase was primarily driven by non-recurring revenue recognized upon achievement of the Pol Theta preclinical development milestone, GSK’s waiver of its option related to MAT2A program and an increase in collaboration revenue for R&D services performed related to the Pol Theta and Werner Helicase programs. Generally, revenue recognition related to the GSK Collaboration Agreement, including as related to the previously received upfront payment or to certain development milestone payments, may vary considerably by period and certain components thereof may generally decrease year-over-year as we satisfy remaining performance obligations, for example, relating to the Pol Theta and WRN R&D Services.

Research and development (R&D) expenses for the three months ended September 30, 2022 totaled $22.4 million compared to $22.8 million for the three months ended June 30, 2022. The decrease was primarily due to lower clinical trial and external research expenses, partially offset by higher consulting expenses.

General and administrative (G&A) expenses for the three months ended September 30, 2022 totaled $6.7 million compared to $5.6 million for the three months ended June 30, 2022. The increase was primarily due to higher operational, consulting and personnel-related expenses.

The net income for the three months ended September 30, 2022 was $1.6 million compared to the net loss of $22.1 million for the three months ended June 30, 2022. Total stock compensation expense for the three months ended September 30, 2022 was $3.0 million compared to $3.0 million for the three months ended June 30, 2022.

On November 8, 2022 ARS Pharmaceuticals, Inc. (Nasdaq: SPRY) (ARS or the Company), a biopharmaceutical company dedicated to empowering at-risk patients and caregivers to better protect themselves from severe allergic reactions that could lead to anaphylaxis, reported the closing of its merger with Silverback Therapeutics, Inc. (Silverback) (Press release, Silverback Therapeutics, NOV 8, 2022, View Source [SID1234623421]). This follows the satisfaction of all customary closing conditions, including approval of the merger by the stockholders of Silverback. The combined company will operate as ARS Pharmaceuticals, Inc., and shares of its common stock will commence trading under the trading symbol "SPRY" on November 9, 2022, on the Nasdaq Global Select Market. Effective as of the closing of the merger, ARS has over $280 million in cash and marketable securities.

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ARS has designed and developed neffy to provide injection-like absorption of epinephrine, in a small, easy-to-carry, easy-to-use, rapidly administered, and reliable nasal spray device for the treatment of Type I severe allergic reactions, including anaphylaxis. With its needle-free administration, neffy may help eliminate the anxiety and hesitation associated with using an epinephrine injection device.

The Company’s New Drug Application (NDA) submission for neffy is currently under review by the U.S. Food and Drug Administration (FDA) with an anticipated Prescription Drug User Fee Act (PDUFA) date in mid-2023. ARS has also filed and cleared validation of a Marketing Authorization Application (MAA) in Europe, which is currently under review by the European Medicines Agency (EMA).

"This is a transformative time for ARS, enabling our move to a publicly traded organization and providing important resources to support the potential launch and commercialization of neffy, upon approval," said Richard Lowenthal, co-founder, president and CEO of ARS. "Millions of individuals suffer from severe allergic reactions, and unfortunately, too many do not treat their symptoms in time or at all with injection devices, leading to disease progression and potentially dangerous or life-threatening outcomes. With neffy, our goal is to eliminate the fear of administering epinephrine with a small, needle-free and easy-to-use nasal spray. Our team at ARS believes that neffy can add significant clinical value to the community by providing an alternative to the currently approved injection devices for patients and caregivers that either do not carry, avoid using or hesitate to use their epinephrine injection device. With the funding from our merger with Silverback, ARS is also dedicated to significant efforts on patient education and support of advocacy groups working to protect the community of allergy patients with this disease."

Post-merger, ARS has approximately 94 million shares of common stock outstanding. Prior ARS equityholders collectively own approximately 62% of the combined company and prior Silverback equityholders collectively own approximately 38% of the combined company, in each case on a fully diluted basis using the treasury stock method and excluding out-of-the-money options of Silverback.

Effective as of the closing of the merger, the board of directors of ARS (Board) will be comprised of eleven directors, including three directors of Silverback:

Pratik Shah, Ph.D., chairman of the Board;

Rajeev Dadoo, Ph.D., managing partner, SR One Capital Management, L.P.;

Saqib Islam, J.D. chief executive officer of Springworks Therapeutics, Inc.;

Michael Kelly, former president of U.S. operations for Adapt Pharma, Inc.;

Peter Kolchinsky, Ph.D., managing partner, RA Capital Management, L.P.;

Jonathan Leff, partner, Deerfield Management and chairman of the Deerfield Institute;

Richard Lowenthal, M.Sc., MSEL, co-founder, president and chief executive officer of ARS;

Brent Saunders, executive chairman of The Beauty Health Company

Phillip Schneider, board member of Longboard Pharmaceuticals Inc., former chief financial officer & senior vice president of IDEC Pharmaceuticals Corporation;

Laura Shawver, Ph.D., chief executive officer of Capstan Therapeutics and former chief executive officer of Silverback;

Peter Thompson, M.D., private equity partner at Orbimed Advisors LLC.

SVB Securities LLC acted as financial advisor to Silverback, and Cooley LLP served as legal counsel to Silverback for the merger. Inceptiv Law served as legal counsel to ARS for the merger.

About Type I Allergic Reactions including Anaphylaxis

Type I severe allergic reactions are serious and potentially life-threatening events that can occur within minutes of exposure to an allergen and require immediate treatment with epinephrine, the only FDA-approved medication for these reactions. While epinephrine autoinjectors have been shown to be highly effective, there are well published limitations that result in many patients and caregivers delaying or not administering treatment in an emergency situation. These limitations include fear of the needle, lack of portability, needle-related safety concerns, lack of reliability, and complexity of the devices. There are approximately 25 to 40 million people in the United States who experience Type I severe allergic reactions. Of those, only 3.3 million currently have an active epinephrine autoinjector prescription, and of those, only half consistently carry their prescribed autoinjector. Even if patients or caregivers carry an autoinjector, more than half either delay or do not administer the device when needed in an emergency.

On November 8, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that the U.S. Food and Drug Administration (FDA) has approved the PD-1 inhibitor Libtayo (cemiplimab-rwlc) in combination with platinum-based chemotherapy for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with no EGFR, ALK or ROS1 aberrations (Press release, Regeneron, NOV 8, 2022, View Source [SID1234623420]). Patients must either have metastatic or locally advanced tumors that are not candidates for surgical resection or definitive chemoradiation. Patients may be treated with this combination irrespective of PD-L1 expression or histology.

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"This second FDA approval for cemiplimab-rwlc in advanced non-small cell lung cancer greatly broadens the scope in which a cemiplimab-rwlc-based regimen can be prescribed to encompass a wide range of patients, either as single agent in those with PD-L1 ≥50% or now in combination with chemotherapy irrespective of PD-L1 expression or tumor histology," said David R. Gandara, M.D., Professor Emeritus and Senior Advisor of the Thoracic Oncology Program at the University of California Davis Comprehensive Cancer Center. "The approval is based on a Phase 3 trial designed to closely resemble a patient population with varied disease presentations that physicians manage in everyday clinical practice. Even with these diverse disease presentations, cemiplimab-rwlc combined with chemotherapy demonstrated a marked increase in overall survival, at a median of 22 months versus 13 months with chemotherapy alone. Clearly, this is an advance which is clinically meaningful for our patients with advanced stage non-small cell lung cancer."

The FDA approval is based on data from the global Phase 3 trial, EMPOWER-Lung 3, that investigated Libtayo in combination with a physician’s choice of platinum-doublet chemotherapy (Libtayo combination), compared to platinum-doublet chemotherapy alone. The trial enrolled 466 patients with locally advanced or metastatic NSCLC, irrespective of PD-L1 expression or tumor histology, and with no ALK, EGFR or ROS1 aberrations. Among those enrolled, 43% had tumors with squamous histology, 67% had tumors with <50% PD-L1 expression, 15% had inoperable locally advanced disease not eligible for definitive chemoradiation, and 7% had pretreated and clinically stable brain metastases.

"Libtayo is now approved for extending the survival of patients with advanced non-small cell lung cancer as both a monotherapy in high PD-L1 expressors and in combination with chemotherapy irrespective of PD-L1 expression levels, achieving a high bar that has only been met by one other PD-1 targeting agent," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "With this FDA approval, Libtayo can expand its role as a key treatment option for advanced non-small lung cancer, in addition to serving as a standard-of-care for two advanced non-melanoma skin cancers. We are committed to investigating Libtayo through ongoing trials as a monotherapy and as a backbone of combination treatments in multiple cancers. We thank the many investigators, patients and their families who have participated in our pivotal trials."

Efficacy in EMPOWER-Lung 3 was assessed in 466 patients who were randomized 2:1 to receive either Libtayo 350 mg (n=312) or placebo (n=154) intravenously every 3 weeks, plus histology-specific platinum-doublet chemotherapy. The trial was stopped early based on a recommendation by the Independent Data Monitoring Committee after the Libtayo combination demonstrated a significant improvement in overall survival (OS), the primary endpoint. Efficacy results comparing the Libtayo combination to chemotherapy alone showed a:

22-month median OS versus 13 months, representing a 29% relative reduction in the risk of death (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.53 to 0.93; p=0.014). The 12-month probability of survival was 66% for the Libtayo combination versus 56% for chemotherapy, per Kaplan-Meier estimates.
8-month median PFS versus 5 months, representing a 44% reduction in the risk of disease progression (HR: 0.56; 95% CI: 0.44 to 0.70; p<0.0001). The 12-month probability of PFS for the Libtayo combination was 38% versus 16% for chemotherapy.
43% overall response rate versus 23%.
16-month median DOR (range: 2 to 19+) versus 7 months (range: 2 to 19+).
Safety was assessed in 312 patients in the Libtayo combination group (median duration of exposure: 38 weeks) and 153 patients in the chemotherapy group (median duration of exposure: 21 weeks). The most common adverse reactions occurring in >15% of patients were alopecia (37% Libtayo combination, 43% placebo), musculoskeletal pain (30% Libtayo combination, 36% placebo), nausea (25% Libtayo combination, 16% placebo), fatigue (23% Libtayo combination, 18% placebo), peripheral neuropathy (23% Libtayo combination, 19% placebo) and decreased appetite (17% Libtayo combination, 12% placebo). Serious adverse reactions occurred in 25% of patients, with treatment discontinuations due to adverse reactions in 5% and fatal adverse reactions in 6%. No new Libtayo safety signals were observed.

"The approval of Libtayo in the combination setting builds on the monotherapy indication in advanced non-small cell lung cancer and furthers our excitement for what’s to come as we continue our potentially transformative oncology research," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "Libtayo is the backbone of our oncology strategy, designed to synergistically combine multiple modalities to provide more options for more patients. We look forward to delivering on the promise of our research in other meaningful combinations that leverage Libtayo and our homegrown pipeline of investigational bispecific antibodies."

"We welcome this latest approval for Libtayo as a first-line combination treatment for appropriate patients with advanced lung cancer," said Andrea Ferris, President and CEO at the LUNGevity Foundation. "Lung cancer remains one of the most common cancers worldwide, and every new treatment option is an important step forward against this deadly cancer."

About Non-small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death worldwide. In recent years, more than 236,000 and 2.2 million annual new cases have been diagnosed in the U.S. and globally, respectively. Approximately 84% of all lung cancers are NSCLC, with 75% of these cases diagnosed in advanced stages. Additionally, 70% of all NSCLC cases will have <50% PD-L1 expression, making it the most common treatment setting.

About Libtayo
Libtayo is a fully human monoclonal antibody targeting the immune checkpoint receptor PD-1 on T-cells and was invented using Regeneron’s proprietary VelocImmune technology. By binding to PD-1, Libtayo has been shown to block cancer cells from using the PD-1 pathway to suppress T-cell activation. In the U.S. and other countries Libtayo is indicated in certain patients with advanced basal cell carcinoma (BCC), advanced cutaneous squamous cell carcinoma (CSCC) and advanced NSCLC, as well as in advanced cervical cancer in Canada and Brazil. As of July 1, 2022, Libayo is developed and marketed globally by Regeneron.

In the U.S., the generic name for Libtayo in its approved indications is cemiplimab-rwlc, with rwlc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the FDA. Outside of the U.S., the generic name of Libtayo in its approved indication is cemiplimab.

The extensive clinical program for Libtayo is focused on difficult-to-treat cancers. Libtayo is currently being investigated in trials as a monotherapy, as well as in combination with either conventional or novel therapeutic approaches for other solid tumors and blood cancers. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.

U.S. FDA-approved Indications
Libtayo is a prescription medicine used to treat:

People with a type of skin cancer called advanced cutaneous squamous cell carcinoma (CSCC) that has spread or cannot be cured by surgery or radiation.
People with a type of skin cancer called basal cell carcinoma (BCC):
That cannot be removed by surgery (locally advanced BCC) and have received treatment with a hedgehog pathway inhibitor (HHI), or cannot receive treatment with an HHI.
That has spread (metastatic BCC) and have received treatment with an HHI, or cannot receive treatment with an HHI. This use is approved based on how many patients responded to treatment and how long they responded. Studies are ongoing to provide additional information about clinical benefit.
Adults with a type of lung cancer called NSCLC:
Libtayo may be used in combination with chemotherapy that contains a platinum medicine as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor does not have an abnormal "EGFR", "ALK" or "ROS1" gene.
Libtayo may be used alone as your first treatment when your lung cancer has not spread outside your chest (locally advanced lung cancer) and you cannot have surgery or chemotherapy with radiation, OR your lung cancer has spread to other areas of your body (metastatic lung cancer), AND your tumor tests positive for high "PD-L1", AND your tumor does not have an abnormal "EGFR", "ALK "or "ROS1" gene.
It is not known if Libtayo is safe and effective in children.

IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS

What is the most important information I should know about Libtayo
LIBTAYO is a medicine that may treat certain cancers by working with your immune system. LIBTAYO can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

Lung problems: cough, shortness of breath, or chest pain
Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual, stools that are black, tarry, sticky or have blood or mucus, or severe stomach-area (abdomen) pain or tenderness
Liver problems: yellowing of your skin or the whites of your eyes, severe nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine (tea colored), or bleeding or bruising more easily than normal
Hormone gland problems: headache that will not go away or unusual headaches, eye sensitivity to light, eye problems, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, your voice gets deeper, dizziness or fainting, or changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems: decrease in your amount of urine, blood in your urine, swelling of your ankles, or loss of appetite
Skin problems: rash, itching, skin blistering or peeling, painful sores or ulcers in mouth or nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with LIBTAYO. Call or see your healthcare provider right away for any new or worsening signs or symptoms, which may include: chest pain, irregular heartbeat, shortness of breath or swelling of ankles, confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs, double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight, persistent or severe muscle pain or weakness, muscle cramps, low red blood cells, or bruising
Infusion reactions that can sometimes be severe. Signs and symptoms of infusion reactions may include: nausea, chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feel like passing out, fever, back or neck pain, or facial swelling
Rejection of a transplanted organ. Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had
Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with LIBTAYO. Your healthcare provider will monitor you for these complications
Getting medical treatment right away may help keep these problems from becoming more serious. Your healthcare provider will check you for these problems during your treatment with LIBTAYO. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with LIBTAYO if you have severe side effects.

Before you receive Libtayo, tell your healthcare provider about all your medical conditions, including if you:

have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus
have received an organ transplant
have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic)
have received radiation treatment to your chest area
have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
are pregnant or plan to become pregnant. LIBTAYO can harm your unborn baby
Females who are able to become pregnant:

Your healthcare provider will give you a pregnancy test before you start treatment
You should use an effective method of birth control during your treatment and for at least 4 months after your last dose of LIBTAYO. Talk with your healthcare provider about birth control methods that you can use during this time
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LIBTAYO
are breastfeeding or plan to breastfeed. It is not known if LIBTAYO passes into your breast milk. Do not breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of LIBTAYO when used alone include muscle or bone pain, tiredness, rash, and diarrhea. The most common side effects of LIBTAYO when used in combination with platinum-containing chemotherapy include hair loss, muscle or bone pain, nausea, tiredness, numbness, pain, tingling, or burning in your hands or feet, decreased appetite. These are not all the possible side effects of LIBTAYO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to Regeneron Pharmaceuticals at 1-877-542-8296.

Please see full Prescribing Information, including Medication Guide.

About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron’s co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create approximately one in five of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV (casirivimab and imdevimab), Dupixent (dupilumab), Libtayo, Praluent (alirocumab), Kevzara (sarilumab), Evkeeza (evinacumab-dgnb) and Inmazeb (atoltivimab, maftivimab and odesivimab-ebgn).

On November 8, 2022 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, reported financial results for the quarter ended September 30, 2022 and provided recent business highlights (Press release, Shattuck Labs, NOV 8, 2022, View Source [SID1234623419]).

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"We are pleased to have completed the monotherapy dose-escalation trial with SL-172154 in platinum-resistant ovarian cancer and to have advanced to the combination phase of clinical development for SL-172154 in both platinum-resistant ovarian cancer and AML and HR-MDS," said Taylor Schreiber, M.D., Ph.D., and Chief Executive Officer of Shattuck. "This year we have significantly expanded our clinical trial footprint to enable steady execution of our clinical studies and are looking forward to the opportunity for SL-172154 to differentiate from other CD47 inhibitors over the course of a data-rich 2023. Beyond our clinical-stage product candidates, we have progressed our gamma delta T cell engager (GADLEN) platform and published key preclinical data which will guide our clinical strategy. We expect to provide additional updates later this month at the SITC (Free SITC Whitepaper) annual meeting."

Third Quarter 2022 Recent Business Highlights and Other Recent Developments

ARC Clinical-Stage Pipeline and Preclinical Pipeline

SL-172154 (SIRPα-Fc-CD40L) Program Update

Completed Enrollment and Study Objectives in Phase 1 Monotherapy Dose-Escalation Clinical Trial of SL-172154 in Platinum-Resistant Ovarian Cancer: This open-label, multi-center, dose-escalation clinical trial evaluated the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered intravenously in patients with advanced platinum-resistant ovarian cancer. We reached a maximum administered dose of 10.0 mg/kg and completed enrollment of additional patients at 3.0 mg/kg with an extended infusion time. We expect to present complete dose-escalation data from the trial midyear 2023.
First Patient Dosed in Combination Trial of SL-172154 with Liposomal Doxorubicin in Advanced Platinum-Resistant Ovarian Cancer: Enrollment is continuing in this trial, which is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154, starting at 3.0 mg/kg, in combination with liposomal doxorubicin in patients with advanced platinum-resistant ovarian cancer. We expect to present initial data from the trial midyear 2023.
Enrollment Progressing in Phase 1A/B Clinical Trial of in SL-172154 in AML and HR-MDS: This trial is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity, and pharmacodynamic effects of SL-172154 as both monotherapy and in combination with azacitidine in a parallel staggered dose escalation. Patients have been dosed in the initial monotherapy cohorts of this trial and enrollment in the azacitidine combination cohorts is expected to begin in the fourth quarter of 2022. Initial dose-escalation data from both monotherapy and azacitidine combination cohorts are expected in the first half of 2023.
SL-279252 (PD1-Fc-OX40L)

Continued Enrollment of SL-279252 Phase 1 Dose-Escalation Clinical Trial in Advanced Solid Tumors: Enrollment of patients with primarily PD-L1 selected tumors continues in the Phase 1 open-label, multi-center, dose-escalation clinical trial to evaluate the safety, tolerability, pharmacokinetics, anti-tumor activity and pharmacodynamic effects of SL-279252 in patients with advanced solid tumors and lymphoma. Top-line data from the Phase 1 trial are anticipated in the first quarter of 2023.
GADLEN

Preclinical Candidates from GADLEN Platform Continue to Advance: We have developed both CD20-directed and B7H3-directed GADLEN product candidates. Additional preclinical data on both programs will be presented at the annual SITC (Free SITC Whitepaper) conference in November. We plan to provide additional clinical development detail and further program guidance in 2023.
Upcoming Events

37th Annual SITC (Free SITC Whitepaper) Annual Meeting: Updated preclinical data on Gamma Delta T Cell Engager (GADLEN) platform candidates to be presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting taking place in Boston on November 8-12, 2022.
Cowen’s 6th Annual IO Next Summit: Management will participate in a fireside chat with covering analyst Marc Frahm at Cowen’s Annual IO Next Conference taking place virtually on November 11, 2022.
5th Annual Evercore ISI HealthCONx Conference: Management will participate in investor one-on-one meetings and a fireside chat with covering analyst Jonathan Miller at the Evercore ISI HealthCONx Conference taking place virtually on November 30 – December 1, 2022.
34th Annual Piper Sandler Healthcare Conference: Management will participate in investor one-on-one meetings and present a corporate update at the Annual Piper Sandler Healthcare Conference taking place in New York City on November 29 – December 1, 2022.
Live and archived audio webcasts of the fireside chats and presentation will be available on the Events & Presentations section of the Company’s website.
Third Quarter 2022 Financial Results

Cash Position: As of September 30, 2022, cash and cash equivalents and investments were $185.1 million, as compared to $268.8 million as of December 31, 2021.
Research and Development (R&D) Expenses: R&D expenses for the quarter ended September 30, 2022 were $18.9 million, as compared to $15.1 million for the quarter ended September 30, 2021. This increase was primarily driven by increases in clinical costs, including clinical site and contract research organization costs, to support clinical development of SL-172154, lab supplies, and personnel-related costs.
General and Administrative (G&A) Expenses: G&A expenses for the quarter ended September 30, 2022 were $6.6 million, as compared to $4.3 million for the quarter ended September 30, 2021. This increase was primarily driven by a litigation settlement of $1.4 million and increases in personnel-related and other operating costs.
Net Loss: Net loss was $24.6 million for the quarter ended September 30, 2022, or $0.58 per basic and diluted share, as compared to a net loss of $17.4 million for the quarter ended September 30, 2021, or $0.41 per basic and diluted share.
2022 Financial Guidance

Shattuck believes its cash and cash equivalents and investments will be sufficient to fund its operations into the second half of 2024, beyond results from its Phase 1 clinical trials of SL-172154 and SL-279252. This cash runway guidance is based on the Company’s current operational plans and excludes any addition funding that may be received, proceeds from business development transactions, or additional costs associated with clinical development activities that may be undertaken.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational ARC fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Phase 1 clinical trials are ongoing for patients with advanced platinum-resistant ovarian cancer (NCT05483933) and patients with AML and HR-MDS (NCT05275439).

About SL-279252

SL-279252 (PD1-Fc-OX40L) is an investigational ARC fusion protein designed to simultaneously inhibit the PD-1/PD-L1 interaction and activate the OX40 receptor in patients with advanced cancers. A Phase 1 trial in patients with solid tumors and lymphoma is ongoing (NCT03894618).

On November 8, 2022 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported its financial results for the quarter ended September 30, 2022, its recent business highlights, and a preview of select anticipated milestones (Press release, Sutro Biopharma, NOV 8, 2022, View Source [SID1234623418]).

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"We are pleased with the productivity and potential of our cell-free platform, as demonstrated most recently by Vaxcyte’s positive topline data readout for its 24-valent pneumococcal conjugate vaccine, VAX-24," said Bill Newell, Sutro’s Chief Executive Officer. "We feel confident in the ability of our platform to generate additional value and capital, as exemplified by the iADC collaboration with Astellas. As we look towards the end of the year, we are on track to present the STRO-002 Phase 1 dose-expansion data and expect to be disclosing the study design on a registration-enabling Phase 2 study for patients with advanced ovarian cancer."

Recent Business Highlights and Select Anticipated Milestones
STRO-002, FolRα-Targeting ADC: STRO-002 is being studied in the clinic, in both the U.S. and Europe, for patients with ovarian and endometrial cancers.

Data demonstrating the anti-leukemic activity of STRO-002 for pediatric patients with relapsed/refractory CBF2AT3-GLIS2 acute myeloid leukemia (AML) treated under ongoing compassionate use will be presented on December 10, 2022 at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2022) as an oral presentation. CBF2AT3-GLIS2 (CBF/GLIS) is a highly refractory and uniformly fatal oncogenic fusion and the underlying genomic cause of "RAM" phenotype AML, a megakaryoblastic leukemia subtype seen exclusively in infants and young children.
Abstract Title: Anti-Leukemic Activity of STRO-002 a Novel Folate Receptor-α (FR-α)-Targeting ADC in Relapsed/Refractory CBF2AT3-GLIS2 AML

Session: Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Relapsed/Refractory AML

Date: Saturday, December 10, 2022

Session Time: 9:30 a.m. – 11:00 a.m. CST

Presentation Time: 10:45 a.m. CST

The accepted ASH (Free ASH Whitepaper) abstract is available at (View Source), and a Sutro-authored whitepaper with details about this rare indication and Sutro’s compassionate use program is available at (View Source).

Sutro expects to report additional data on efficacy, safety, and durability from the Phase 1 dose-expansion cohort in patients with advanced ovarian cancer, together with the design of a registration-enabling Phase 2 study, by the end of 2022.
Discussions with the FDA on a registrational study for patients with advanced ovarian cancer were held mid-year 2022, in which the agency signaled that an accelerated approval pathway could be available for STRO-002 in a platinum-resistant ovarian cancer patient population.
Additional ongoing clinical studies for STRO-002 include a combination study with bevacizumab for patients with advanced ovarian cancer and a dose-expansion study for patients with endometrial cancer.
STRO-001, CD74-Targeting ADC: The Phase 1 study for patients with B‑cell malignancies, including patients withnon-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM), continues in dose escalation.

Dose escalation is ongoing to achieve a recommended Phase 2 dose (RP2D), with the last reported doses of 5.0 mg/kg in the MM cohort and 5.0 mg/kg in the NHL cohort.
Sutro’s partner BioNova Pharma (BioNova) is advancing clinical development of BN301 (STRO-001) for patients with hematological malignancies in Greater China. In September 2022, BioNova announced that the Center of Drug Evaluation of the National Medical Products Administration of China had approved its investigational new drug (IND) application for BN301 (STRO-001) to conduct clinical trials in patients with hematologic malignancies in China.
Additional Pipeline Programs: A Sutro Research Forum highlighted STRO-003 and Sutro’s emerging research portfolio.

STRO-003 is an optimally designed ADC targeting ROR1, with eight precisely positioned β-Glucuronidase-cleavable linkers attached to next-generation exatecan warheads, which inhibit topoisomerase-1 resulting in DNA disruption.
Patient-derived xenograft models (PDX) have shown potent cell killing by STRO-003 in low antigen expressing tumors; and STRO-003 has shown encouraging tolerability in preclinical rodent and non-human primate studies.
Sutro provided details on its product and process design, which enables its emerging portfolio including novel therapeutic modalities—for example, a single antibody which can be conjugated site-specifically with two different payloads with synergistic mechanisms.
Collaboration Updates: Sutro continues to seek to maximize the value of its proprietary cell-free platform by working with partners on programs in multiple disease spaces and geographies and has generated from collaborators an aggregate of approximately $600 million in cash through September 30, 2022, which includes payments and equity investments.

In October 2022, Vaxcyte reported positive topline data from the Phase 1/2 proof-of-concept study of its 24-valent pneumococcal conjugate vaccine candidate (VAX-24) under investigation for the prevention of invasive pneumococcal disease in adults aged 18-64. Under an existing license agreement with Vaxcyte, Sutro is eligible to receive four percent (4%) royalties on worldwide net sales of VAX-24 and any licensed vaccine candidates.
In June 2022, Sutro entered into a collaboration with Astellas on the discovery and development of immunostimulatory antibody-drug conjugates (iADCs) for three targets, including an upfront payment to Sutro of $90 million received in July 2022, and $422.5 million in potential milestones per product candidate. Sutro will also receive financial support for its research efforts and has an option to co-develop and co-commercialize product candidates in the U.S.
A $10 million milestone payment from Merck was triggered in July 2022 upon the first patient dosed in a Phase 1 study of MK-1484, a selective IL-2 agonist, under the 2018 cytokine derivative collaboration.
Sutro is manufacturing initial drug supply for the clinical development of Merck’s MK-1484, currently in a Phase 1; clinical trial materials for Bristol Myers Squibb’s (BMS) CC-99712, a BCMA‑targeting ADC for treatment of multiple myeloma, currently in Phase 1; and clinical trial materials for M1231, a MUC1-EGFR-targeting bispecific ADC, for Merck KgaA, Darmstadt, Germany, known as EMD Serono in the U.S. and Canada (EMD Serono), also currently in Phase 1.
Sutro is providing clinical drug supply to BioNova for clinical studies for BN301 (STRO-001) in Greater China. Sutro is currently supporting Tasly Biopharmaceuticals (Tasly) for initiation of clinical development activities and an IND filing in Greater China for STRO-002 and will provide initial clinical drug supply.
Third Quarter 2022 Financial Highlights
Cash, Cash Equivalents and Marketable Securities
As of September 30, 2022, Sutro had cash, cash equivalents and marketable securities of $287.3 million, ascompared to $191.6 million as of June 30, 2022, providing a projected cash runway into the first half of 2024, based on current business plans and assumptions. The above balances do not include the value associated with Sutro’s holdings of Vaxcyte common stock.

Unrealized Gain from Increase in Value of Vaxcyte Common Stock
As of September 30, 2022, Sutro held approximately 1.5 million shares of Vaxcyte common stock, with a fair value of $36.9 million. The non-operating, unrealized gain of $3.5 million in the third quarter of 2022 was due to the increase since June 30, 2022 in the estimated fair value of Sutro’s holdings of Vaxcyte common stock. Vaxcyte common stock held by Sutro will be remeasured at fair value based on the closing price of Vaxcyte’s common stock on the last trading day of each reporting period, with any non-operating, unrealized gains and losses recorded in Sutro’sstatements of operations. Sutro sold approximately 1 million shares of Vaxcyte common stock at fair market value during the period from October 1, 2022 through November 7, 2022.

Revenue
Revenue was $25.1 million for the quarter ended September 30, 2022, as compared to $8.5 million for the same period in 2021, related principally to recognition of the milestone payment from Merck and the Astellas, BMS, and EMD Serono collaborations in 2022 and the Merck, BMS, and EMD Serono collaborations in 2021. Future collaboration and license revenue from Astellas, Merck, BMS, EMD Serono, Tasly, and BioNova, and from anyadditional collaboration and license partners, will fluctuate as a result of the amount and timing of revenue recognitionof upfront, milestones, and other agreement payments.

Operating Expenses
Total operating expenses for the quarter ended September 30, 2022 were $46.4 million, as compared to $43.2 million for the same period in 2021. The third quarter of 2022 includes non-cash expenses for stock-based compensation of $6.8 million and depreciation and amortization of $1.4 million, as compared to $6.5 million and $1.1 million, respectively, in the comparable 2021 period. Total operating expenses for the quarter ended September 30, 2022 were comprised of research and development expenses of $31.7 million and general and administrative expenses of $14.6 million, which are expected to increase in 2022 as Sutro’s internal product candidates advance in clinical development and additional general and administrative expenses are incurred as a public company.