On November 8, 2022 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next generation therapeutics for cancer patients, reported financial results for the third quarter ended September 30, 2022 and provided recent business updates (Press release, Sensei Biotherapeutics, NOV 8, 2022, View Source [SID1234623430]).

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"We believe VISTA has tremendous potential as an immune checkpoint target and have prioritized the advancement of SNS-101 toward clinical studies. This has been a productive quarter in that regard highlighted by robust and differentiated preclinical data, which we believe demonstrate the potential of SNS-101 to avoid poor pharmacokinetics from target-mediated drug disposition and lower the risk of cytokine release syndrome, while significantly enhancing the anti-tumor effects of PD-1 blockade. These data, coupled with the progress of our SNS-102 program targeting VSIG4, also support the biological rationale for Sensei’s conditionally active approach as a mechanism for achieving selective activation in the tumor microenvironment. We believe our TMAb platform has the potential to unlock previously undruggable immune targets by avoiding on-target/off-tumor effects that have thwarted previous efforts to inhibit targets such as VISTA," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "With cash runway into the first quarter of 2025, Sensei is well positioned to advance multiple programs and achieve critical near-term milestones, including the anticipated submission of an IND for SNS-101 in the first half of 2023."

Highlights and Milestones

SNS-101

Sensei continues to advance SNS-101, a conditionally active antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation), which is implicated in resistance to PD-1/PD-L1 therapy and correlates with poor survival across numerous cancers. Recent updates for SNS-101 include:

On Friday, November 11, 2022, Sensei will present new preclinical data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held in Boston, MA.
The Company presented preclinical data at the Sixth Annual CRI-ENCI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival which demonstrated SNS-101’s favorable pharmacokinetic (PK) profile in single-dose mouse and non-human primate (NHP) models, and evidence of enhanced anti-tumor effects in combination with anti-PD-1 antibodies in mice. Additionally, SNS-101 demonstrated a superior cytokine release profile compared to a non-pH-sensitive VISTA antibody.
The Company intends to present new data from a multi-dose pharmacokinetic (PK) and toxicology model in non-human primates in the first half of 2023.
Over the last quarter, Sensei completed GMP manufacturing of SNS-101 bulk drug substance and projects sufficient drug product for its planned Phase 1/2 clinical trial.
The Company is exploring ways to leverage SNS-101’s high selectivity for the tumor microenvironment through other modalities.
Sensei remains on track to submit an Investigational New Drug application (IND) for SNS-101 in the first half of 2023.
SNS-102

Sensei is advancing several pH-sensitive antibodies targeting VSIG4 (V-Set and Immunoglobulin Domain Containing 4), a B7-family related protein that is a potent inhibitor of T cell activity and is frequently overexpressed on tumor-associated macrophages. The Company intends to optimize toward a pH-dependent, high-affinity inhibitory antibody that binds VSIG4 selectively in the tumor microenvironment without affecting healthy tissue.

On Thursday, November 10, 2022, Sensei will present a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting detailing an enhanced mechanistic understanding of VSIG4 to inform future antibody development.
The Company has identified eight parental pH-selective VSIG4 antibodies, and a lead antibody set is currently undergoing further optimization.
Sensei remains on track to select a product candidate for SNS-102 in 2023.
SNS-103

Sensei is advancing conditionally active antibodies targeting ENTPDase1 (ecto-nucleoside triphosphate diphosphohydrolase-1, also known as CD39), the upstream, rate-limiting enzyme that leads to the breakdown of extracellular ATP and the production of immunosuppressive adenosine. The Company began screening the first set of parental antibodies in September 2022 and remains on track to select a product candidate in 2023.

Corporate Updates

On Monday, November 21, 2022, Sensei will host a virtual KOL webinar "Lessons from VISTA: New Strategies to Address an Important Immune Checkpoint." Robert Schreiber, Ph.D., a globally recognized expert on the immune system’s role in anti-cancer immunity, will present on VISTA’s role in immunosuppression, and Sensei management will provide a review of the SNS-101 program.
Sensei will present at the 13th Annual Jefferies Global Healthcare Conference, being held in London, United Kingdom, on Thursday, November 17, 2022, at an updated time of 8:00 a.m. GMT.
Consistent with the Company’s prioritization of its TMAb platform, Sensei has suspended development efforts related to its ImmunoPhage platform, including its SNS-401-NG product candidate. As a result, the Company now plans to focus all its resources and efforts on developing conditionally active antibodies through its TMAb platform.
Third Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $116.6 million as of September 30, 2022, as compared to $147.6 million as of December 31, 2021. Sensei expects its current cash balance to fund operations into the first quarter of 2025.

Research and Development (R&D) Expenses: R&D expenses were $9.2 million for the quarter ended September 30, 2022, compared to $6.4 million for the quarter ended September 30, 2021. The increase in R&D expenses was primarily attributable to increased manufacturing and early development activities for the Company’s lead program SNS-101, partially offset by a decrease in clinical trial expenses.

General and Administrative (G&A) Expenses: G&A expenses were $4.8 million for the quarter ended September 30, 2022, compared to $3.9 million for the quarter ended September 30, 2021. The increase in G&A expense was primarily attributable to external professional services.

Net Loss: Net loss was $13.4 million for the quarter ended September 30, 2022, compared to $9.7 million for the quarter ended September 30, 2021.

On November 8, 2022 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical-stage company developing a portfolio of immune-educating therapies based on its novel DPX platform to treat solid and hematologic cancers, reported that it will hold a conference call and webcast on Friday, November 11, 2022, at 8:00 a.m. ET to discuss the company’s 2022 third quarter financial and operational results (Press release, IMV, NOV 8, 2022, View Source [SID1234623428]).

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Financial analysts are invited to join the conference call by registering at this link prior the call to receive their individual dial-in information.

Other interested parties will be able to access the live audio webcast by registering on IMV website: View Source The webcast will be recorded and will then be available on the IMV website for 30 days following the call.

On November 8, 2022 Instil Bio, Inc. ("Instil") (NASDAQ: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported poster presentations of pre-clinical data and trial-in-progress for the ongoing ITIL-306 Phase 1 clinical trial using the CoStimulatory Antigen Receptor (CoStAR) platform at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), to be held from November 8-12, 2022 (Press release, Instil Bio, NOV 8, 2022, View Source [SID1234623427]).

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Pre-clinical data demonstrating the activity of CoStAR across physiologically-relevant ranges of FRα expression and TCR affinity are featured in Poster 282. These data demonstrated that CoStAR amplified T-cell responses at all FRα expression levels as long as FRα was expressed, supporting the clinical exploration of ITIL-306 in multiple solid tumor types with a variety of FRα expression levels. Furthermore, CoStAR-expressing cells do not respond to FRα in the absence of TCR stimulation, underscoring the expected safety profile of the CoStAR platform. Currently, ITIL-306 is being evaluated in a first-in-human Phase 1 dose escalation clinical study for treatment of refractory solid tumors with the first patient dosed in October 2022.

The company also is presenting a trial-in-progress poster summarizing the design of the ongoing Phase 1 study of ITIL-306 (Poster 776). ITIL-306-201 is a Phase 1 multicenter, single-arm, dose escalation and expansion study evaluating the safety and feasibility of ITIL-306 in adult patients with advanced epithelial ovarian cancer (EOC), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) who relapsed from or are refractory to ≥1 prior line of systemic therapy. Importantly, the Phase 1 study of ITIL-306 features a treatment regimen free of high-dose interleukin-2.

Details of the poster presentations are as follows:

Title: Anti-folate receptor alpha (FRα) CoStimulatory Antigen Receptor (CoStAR) improves T-cell function across physiologically relevant ranges of FRα expression and T-cell receptor (TCR) affinities
Authors: Martina Sykorova, Michelle Mojadidi, Leyuan Bao, Eric Gschweng, Milena Kalaitsidou, Gray Kueberuwa, Xingliang (Tim) Zhou, Rubén Alvarez-Rodríguez, John S. Bridgeman
Poster/Abstract Number: 282

Title: ITIL-306-201: A multicenter, first-in-human phase 1a/1b study of ITIL-306, an engineered autologous tumor-infiltrating lymphocyte (TIL) cell therapy product, in adults with advanced solid tumors
Authors: Jeffrey Ward, Armin Ghobadi, John B. Liao, Adam Schoenfeld, Scott S. Tykodi, Yizhou Jiang, John Le Gall, Ruben Alvarez-Rodriguez, Marika Sherman, Tiffany Singson, Jeff McLeroy
Poster/Abstract Number: 776

The posters are available on the publications section of the Instil Bio website: www.instilbio.com/publications.

On November 8, 2022 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported financial results for the third quarter ended September 30, 2022 and provided a corporate update (Press release, Arvinas, NOV 8, 2022, View Source [SID1234623426]).

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"We made significant progress during the third quarter, including initiating activity to enroll four new clinical trials with ARV-471 and beginning a Phase 2 trial with ARV-766," said John Houston, Ph.D., president and chief executive officer at Arvinas. "We also further strengthened our executive team and Board of Directors as we fully transition to a late-stage development organization. We expect the initiation of two Phase 3 trials with ARV-471 in patients with metastatic breast cancer by the end of this year, and a Phase 3 trial with bavdegalutamide in men with metastatic castrate resistant prostate cancer in the second half of 2023. We look forward to the upcoming presentation on the Phase 2 VERITAC trial with ARV-471 at the San Antonio Breast Cancer Symposium in December, and Arvinas is well-positioned as we move into 2023."

Business Highlights and Recent Developments

Initiated, with Pfizer, multiple clinical trials and enrollment activity with ARV-471 in patients with ER+/HER2- breast cancer:
Phase 1b trial (TACTIVE-E) with ARV-471 + everolimus (ClinicalTrials.gov Identifier NCT05501769)
Phase 1b trial with ARV-471 as a monotherapy in Japanese patients (ClinicalTrials.gov Identifier NCT05463952)
Activity that will enable dosing in 4Q2022 for a Phase 1b umbrella trial (TACTIVE-U) with ARV-471, including a combination arm with abemaciclib (Part A: ClinicalTrials.gov Identifier NCT05548127) and a combination arm with ribociclib (Part B: ClinicalTrials.gov Identifier NCT05573555)
Activity that will enable dosing in 4Q2022 for a Phase 2 trial (TACTIVE-N) with ARV-471 as a monotherapy in the neoadjuvant setting (ClinicalTrials.gov Identifier NCT05549505)
Initiated a Phase 2 trial in metastatic castrate resistant prostate cancer (mCRPC) with ARV-766 (ClinicalTrials.gov Identifier NCT05067140)
Appointed John Young to the Company’s Board of Directors
Appointed Lisa Sinclair as Senior Vice President, Corporate Operations
Appointed Paul McInulty as Senior Vice President, Regulatory Affairs
Executed an agreement with PhoreMost Ltd. to expand the capabilities of our PROTAC Discovery Engine
Executed a research collaboration agreement with Rockefeller University to leverage innovative screening capabilities
Launched inaugural "Arvinas Impact Day," a company-wide community service day benefiting organizations in the Greater New Haven area
Nearly 200 Arvinas employees participated in activities to support important priorities for Arvinas, including science, technology, engineering, and math (STEM) initiatives, and the Greater New Haven and patient communities
Anticipated Upcoming Milestones and Expectations

ARV-471
With Pfizer, the companies plan to:

Initiate Phase 3 trial with ARV-471 + palbociclib as a first-line treatment in patients with metastatic breast cancer (4Q 2022)
Initiate Phase 3 trial with ARV-471 as a second-line treatment in patients with metastatic breast cancer (4Q 2022)
Present data from the VERITAC Phase 2 expansion trial (200 mg and 500 mg) (San Antonio Breast Cancer Symposium, December 2022)
Initiate additional arms of the Phase 1b combination trial (TACTIVE-U) with other targeted therapies (2023)
Present data from the Phase 1b combination trial with palbociclib at a medical conference (1H 2023)
Bavdegalutamide (ARV-110)

Confirm final dose selection and secure final health authority feedback for global Phase 3 trial protocol (1H 2023)
Initiate a global Phase 3 trial in metastatic castration-resistant prostate cancer (mCRPC) for patients with AR T878/H875 tumor mutations (2H 2023)
Complete enrollment in Phase 1b combination study with abiraterone (2H 2023)
ARV-766

Share Phase 1 dose escalation trial data in mCRPC (2Q 2023)
Pipeline:

Present new preclinical neuroscience data at Society for Neuroscience’s "Neuroscience 2022" meeting (Nov. 12-16, 2022): Orally Administered PROTAC Molecules Selectively Clear Pathologic Neurodegenerative Proteins in CNS & Muscle
Submit two investigational new drug (IND)/clinical trial authorization (CTA) applications, one in neurology and one in oncology, by year end 2023 with at least two additional programs in IND- or CTA-enabling studies
Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, restricted cash and marketable securities as of September 30, 2022 is sufficient to fund planned operating expenses and capital expenditure requirements multiple years beyond 2024.

Third Quarter Financial Results

Cash, Cash Equivalents, Restricted Cash and Marketable Securities Position: As of September 30, 2022, cash, cash equivalents, restricted cash and marketable securities were $1,276.2 million as compared with $1,507.1 million as of December 31, 2021. The decrease in cash, cash equivalents, restricted cash and marketable securities of $230.9 million for the nine months ended September 30, 2022 was primarily related to cash used in operating activities of $209.2 million (net of $6.5 million received from two collaborators), unrealized loss on marketable securities of $20.2 million, and the purchase of lab equipment and leasehold improvements of $5.7 million, partially offset by proceeds from the exercise of stock options of $4.2 million.

Research and Development Expenses: Research and development expenses were $77.5 million for the quarter ended September 30, 2022, as compared with $40.6 million for the quarter ended September 30, 2021. The increase in research and development expenses of $36.9 million for the quarter was primarily due to an increase in our continued investment in our platform and exploratory programs of $22.3 million, as well as an increase in expenses related to our AR program of $2.8 million, which includes bavdegalutamide and ARV-766, and our ER program of $11.8 million, which is net of the cost sharing of ARV-471 under the global Pfizer collaboration agreement to develop and commercialize ARV-471 that was initiated in July 2021 (ARV-471 Collaboration Agreement).

General and Administrative Expenses: General and administrative expenses were $20.0 million for the quarter ended September 30, 2022, as compared with $16.0 million for the quarter ended September 30, 2021. The increase of $4.0 million was primarily due to an increase in personnel costs of $2.9 million and professional fees of $2.1 million.

Revenues: Revenues were $30.3 million for the quarter ended September 30, 2022 as compared with $9.3 million for the quarter ended September 30, 2021. Revenue is related to the ARV-471 Collaboration Agreement, the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, and the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017. The increase in revenues of $21.0 million was primarily due to revenue from the ARV-471 Collaboration Agreement.

Income Tax Expense: Income tax expense was $2.2 million for the quarter ended September 30, 2022, as compared with zero for the quarter ended September 30, 2021 due to taxable income projected for fiscal year 2022 primarily related to revenue recognized in 2022 for tax purposes from the ARV-471 Collaboration Agreement.

Net Loss: Net loss was $66.2 million for the quarter ended September 30, 2022, as compared with $46.8 million for the quarter ended September 30, 2021. The increase in net loss for the quarter was primarily due to increased research and development expenses, general and administrative expenses, and income tax expense, partially offset by increased revenue.

About bavdegalutamide (ARV-110)
Bavdegalutamide (ARV-110) is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). Bavdegalutamide is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

Bavdegalutamide has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

About ARV-766
ARV-766 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade AR. In preclinical studies, ARV-766 degraded all resistance-driving point mutations of AR, including L702H, a mutation associated with treatment with abiraterone and other AR-pathway therapies.

ARV-766 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer, and ARV-766 may also have applicability in other AR-driven diseases both in and outside oncology. ARV-766 has demonstrated activity in preclinical models of resistance to currently available AR-targeted therapies.

On November 8, 2022 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Precision Biosciences, NOV 8, 2022, View Source [SID1234623425]).

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"Over the last year, Precision has made considerable progress against our corporate and development objectives. We executed a disciplined portfolio strategy to focus on human therapeutics, advanced our lead clinical stage CAR T programs, leveraged platform partnerships, and made data-informed decisions designed to maximize patient impact and extend our expected cash runway to the end of 2024," said Michael Amoroso, Chief Executive Officer of Precision BioSciences. "We have refined the scope of our CAR T portfolio, focusing on PBCAR0191, known as azer-cel, in the growing CAR T-relapsed population, which has shown high complete response rates, long-term responses, and peak CAR T expansion on par with autologous CAR T in durable responders. We are also exploring the potential of our immune-evading stealth cell technology with PBCAR19B in earlier line DLBCL patients with the goal of displacing autologous CAR T treatment options. Looking ahead, our team is focused on executing and advancing our clinical stage CD19 targeted CAR T programs and providing a clinical update in late Q4 2022 or early Q1 2023, depending on patient accrual and follow-up."

Mr. Amoroso continued, "We also advanced multiple in vivo gene editing programs, independently and with partners, highlighted by our research collaboration with Novartis in June and recent preclinical data shared at ESGCT. As a result of ARCUS’ versatility, recent high efficiency in vivo gene insertion data, and scientific progress with wholly-owned and partnered programs, we have commenced a portfolio review of our in vivo gene editing programs. We are exploring ways to expedite key programs, advance new indications, and maximize ARCUS’ core features which have the potential to enable high efficiency gene insertion and complex edits aimed at restoring genomic function and treating the underlying root cause of specific genetic diseases. Our aim is to focus on programs in which ARCUS is most differentiated and where we see potential for a clear and rapid path to market, while providing a potentially curative therapeutic solution to patients with the highest unmet need. We look forward to providing meaningful progress updates along the way."

Recent Developments and Upcoming Milestones:

Ex Vivo Allogeneic CAR T Portfolio:

PBCAR0191: PBCAR0191, azercabtagene zapreleucel (azer-cel), is Precision’s lead investigational anti-CD19 allogeneic CAR T candidate in a Phase 1/2a clinical trial of adult subjects with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL). An abstract on the cell dose and functional attributes of azer-cel that may be associated with positive safety and efficacy results for CAR T therapy in R/R B-cell lymphoma was accepted for poster presentation at the 64th ASH (Free ASH Whitepaper) Annual Meeting taking place December 10-13, 2022. The poster presentation will highlight the first analysis of an allogeneic CD19 CAR T product composition to demonstrate that strategies intended to maximize stem central memory T-cell fraction (CCR7+) while limiting CD4+ CCR7+ differentiated fraction may improve safety and efficacy of CAR T therapy.

Precision continues dosing subjects with optimized azer-cel CAR T cells in the CAR T relapsed population in which it has shown high and durable complete response rates, while further reducing the dose of lymphodepletion to standard levels in pursuit of best therapeutic index for this patient population.

PBCAR19B: PBCAR19B is Precision’s second generation, anti-CD19 targeting allogeneic CAR T candidate designed to evade immune rejection by host T cell and natural killer (NK) cells with a single-gene edit to knock-down beta-2 microglobulin and insert an HLA-E transgene. Precision continues to recruit patients at Dose Level 2 (flat dose of 540 million cells) with the intent to complete the Phase 1 dose escalation.

Precision expects to provide an update in late Q4 2022 or early Q1 2023, depending on patient accrual and follow-up, on its two distinct CD19 targeted products, including azer-cel which is aiming to achieve a potential first-in-class allogeneic CAR T therapy in the CAR T relapsed population, and PBCAR19B which is seeking to displace autologous CAR T in the second/third line DLBCL population.

PBCAR269A + GSI: PBCAR269A is Precision’s investigational allogeneic CAR T cell candidate targeting B-cell maturation antigen (BCMA) for R/R multiple myeloma in combination with nirogacestat, a gamma secretase inhibitor (GSI) developed by SpringWorks Therapeutics, Inc. The combination therapy and increased dose of PBCAR269A resulted in improved cell expansion, which correlated with increased clinical activity when compared to dose-matched PBCAR269A monotherapy treatment. However, in light of the competitive landscape of BCMA targeted therapies in multiple myeloma, Precision has made the strategic decision not to continue the PBCAR269A clinical program. All subjects enrolled in the study and evaluated for treatment with PBCAR269A and nirogacestat had acceptable tolerability results. While no clinical spending is planned, Precision researchers will evaluate further modifications to the BCMA construct aimed at enabling an allogeneic approach similar to that of autologous CAR T in multiple myeloma. Precision thanks the patients and clinicians for their participation in the PBCAR269A clinical program.

In Vivo Gene Editing Portfolio:

Precision believes that in vivo applications are particularly well suited to ARCUS because they require extremely low levels of off-target editing and efficient delivery. As a gene editing tool, ARCUS can be differentiated by unique attributes which are designed for precise, specific and versatile gene editing. By nature of its origin from a homing endonuclease, ARCUS can be particularly applicable to gene insertion and complex edits designed for gene repair aimed at restoring function, as well as more simple gene knock outs. ARCUS is also unique in its relatively small size which allows delivery to a wider range of cells and tissues using viral and non-viral gene delivery methods.

Novartis In Vivo Gene Editing Collaboration Precision is advancing its gene editing research and development collaboration and license agreement with Novartis to develop a single, custom ARCUS nuclease designed to insert a therapeutic transgene, in vivo, at a "safe harbor" location in the genome. This has the potential to be a one-time transformative treatment option for diseases including certain hemoglobinopathies such as sickle cell disease and beta thalassemia. In conjunction with the close of the agreement, Novartis made a $25 million equity investment in Precision in the second quarter of 2022 and Precision received $50 million in cash in the third quarter of 2022.

Lilly In Vivo Gene Editing Collaboration: Precision continues its in vivo gene editing collaboration with Lilly and is applying ARCUS nucleases for three initial targets, including Duchenne muscular dystrophy in muscle, a central nervous system directed target and a liver directed target.

PBGENE-HBV: Precision’s gene editing program for chronic Hepatitis B applies ARCUS to knock out persistent covalently closed circular DNA (cccDNA) and inactivate integrated hepatitis B genomes, potentially achieving durable HBV S-antigen (HBsAg) loss and reducing viral persistence. Preclinical data from this program were presented during ESGCT in October 2022. Data presented demonstrated that ARCUS efficiently targeted and degraded hepatitis B virus (HBV) cccDNA by 85% and reduced expression of HBsAg by 77% in HBV-infected primary human hepatocytes (PHH). Importantly, the optimized specificity of the ARCUS nuclease completely prevented detectable chromosomal translocations in the PHH model.

PBGENE-PH1: Precision has initiated IND-enabling activities for its PBGENE-PH1 candidate designed to knock out the HAO1 gene as a potential one-time treatment for primary hyperoxaluria type 1 (PH1).

PBGENE-PCSK9: In 2021, Precision initiated a collaboration with iECURE, pursuant to which iECURE is expected to advance Precision’s PBGENE-PCSK9 candidate through preclinical activities as well as a Phase 1 study in familial hypercholesterolemia. As of this date, IND enabling activities for PBGENE-PCSK9 have not been completed. Precision is in discussions with iECURE and will provide an update on the program when more information is available.

Other ARCUS Research:

International Conference on Ureagenesis Defects and Allied Conditions 20221: Preclinical data were presented by researchers from the University of Pennsylvania’s Gene Therapy Program in collaboration with iECURE, Precision’s partner, highlighting an ARCUS-based gene insertion approach for the treatment of ornithine transcarbamylase (OTC) deficiency. Non-human primate (NHP) data demonstrated stable insertion of the therapeutic gene one year post-dosing in newborn and infant NHPs In the follow up data, 12-month biopsies continued to demonstrate construct stability, with transduction efficiency up to 28.2% as measured by in-situ hybridization (ISH). These data further demonstrate the preclinical feasibility of using an ARCUS-mediated gene insertion approach.

ESGCT 29th Congress: Additional abstracts on ARCUS in vivo gene editing were presented in addition to Precision’s HBV program, including one poster presentation each on Precision’s Apolipoprotein C3 and mitochondrial DNA preclinical research.

APOC3 poster presentation: ARCUS gene editing of Apolipoprotein C3 results in substantial reduction in serum triglycerides in vivo
Mito DNA poster presentation: Specific elimination of m.3243A>G mutant mitochondrial DNA using mitoARCUS in cultured cells and a novel xenograft mouse model
Quarter Ended September 30, 2022 Financial Results:

Cash and Cash Equivalents: As of September 30, 2022, Precision had approximately $212.1 million in cash and cash equivalents. The Company expects that existing cash and cash equivalents, expected operational receipts, and available credit will be sufficient to fund its operating expenses and capital expenditure requirements to the end of 2024.

Revenues: Total revenues for the quarter ended September 30, 2022 were $7.4 million, as compared to $24.0 million for the same period in 2021. The decrease of $16.6 million in revenue during the quarter ended September 30, 2022 was primarily the result of the absence of $17.9 million in revenue recognized under the iECURE Agreement in August 2021 subsequent to the full satisfaction of the performance obligation. These decreases in revenue were partially offset by an increase of $3.6 million in revenue recognized under the Novartis Agreement.

Research and Development Expenses: Research and development expenses were $20.0 million for the quarter ended September 30, 2022, as compared to $25.9 million for the same period in 2021. The decrease of $5.9 million was primarily due to a decrease of $3.6 million in external development costs associated with our allogeneic CAR T product candidates, a decrease of $0.9 million in employee-related and other operational costs driven by the separation of Elo in 2021, and a decrease of $1.4 million in clinical manufacturing organization and research costs related to our preclinical studies.

General and Administrative Expenses: General and administrative expenses were $10.3 million for the quarter ended September 30, 2022, as compared to $9.6 million for the same period in 2021. The increase of $0.7 million was primarily due to increased share-based compensation expense.

Other Income and Expense: Total other expense was $1.0 million for the quarter ended September 30, 2022, as compared to total other income of $0.3 million for the same period in 2021.

Net Loss: Net loss was $23.9 million, or $(0.22) per share (basic and diluted), for the quarter ended September 30, 2022, as compared to net loss of $11.3 million, or $(0.19) per share (basic and diluted), for the same period in 2021. Weighted average shares of common stock outstanding were approximately 110.8 million for the quarter ended September 30, 2022, as compared to approximately 59.7 million for the quarter ended September 30, 2021. The increase in weighted average shares of common stock outstanding was primarily due to a $50 million underwritten offering of common stock and Novartis’ $25 million equity investment in the nine months ended September 30, 2022.

Corporate:

Executive Leadership: In September 2022, Cindy Atwell, formerly Senior Vice President of Business Development and Alliance Management, was promoted to Chief Business Officer and continues to oversee the Business Development and Alliance functions with added responsibility for Project and Portfolio Management. Jeff Smith, Ph.D., co-founder and formerly Chief Technology Officer, was promoted to Chief Research Officer and assumed responsibility for the management and direction of the Company’s research programs, reporting directly to the CEO. Derek Jantz, Ph.D., co-founder and Chief Scientific Officer is focusing his time partnering with Michael Amoroso in formulating company strategy and managing relationships with external stakeholders, including current and potential collaboration partners.