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Seagen Names David R. Epstein as Chief Executive Officer and Director

On November 10, 2022 Seagen Inc. (Nasdaq: SGEN) reported that its Board of Directors has appointed David R. Epstein as Chief Executive Officer (CEO) and a member of the Board of Directors (Press release, Seagen, NOV 10, 2022, View Source [SID1234623737]). Mr. Epstein brings more than 30 years of experience in the biopharmaceutical industry, including more than 25 years at Novartis where he built its oncology business unit from initiation to second largest in the world and then served as CEO of Novartis Pharmaceuticals, a division of Novartis AG. More recently, he was executive partner at Flagship Pioneering. In addition, Seagen announced that Roger Dansey, M.D., who has served as Seagen’s Chief Medical Officer (CMO) since 2018 and as Interim CEO since May 2022, has been appointed President, Research and Development. In this new role, Dr. Dansey will continue to serve as CMO reporting to David.

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"Following a comprehensive search process, the Board selected David to serve as Seagen’s next CEO. He shares Seagen’s belief that our future is bright as we continue to build world-class capabilities in order to develop and commercialize new innovative treatments that improve the lives of patients with cancer. David’s demonstrated ability to build and scale a global oncology business, his experience in both large multi-faceted organizations and small biotechnology startups, combined with deep oncology knowledge, provide the strategic and operational expertise needed to lead Seagen to the next level," said Felix J. Baker, Ph.D., Chair of the Board. "We are extremely grateful for Roger’s successful leadership and dedication as interim CEO. We look forward to Roger being able to focus his efforts on further strengthening our early research efforts, as he has successfully done for development, and driving the innovative engine that has been the heart of Seagen to have an even greater impact on cancer patients in the future."

Mr. Epstein said, "I have long admired Seagen as a leader in the development and commercialization of transformative cancer therapies. Seagen is a pioneer in antibody-drug conjugate (ADC) technology with a portfolio of four approved medicines, a diverse pipeline of promising programs, and a science-driven, patient-first culture. I am honored to become CEO and work with the experienced team to further deliver on Seagen’s mission to make a meaningful difference so that people who have been diagnosed with cancer can live better lives."

"I welcome David to the Seagen team and look forward to working closely with him as we continue to bring forward novel ADCs and other targeted treatments for cancer patients," said Dr. Dansey. "I am excited to bring my passion for science and innovation to my expanded role overseeing research and development as we continue to deliver on the full potential of our pipeline and programs."

About David R. Epstein

David R. Epstein has more than 30 years of drug development, deal making, commercialization and people leadership experience on a global scale. Most recently, he was executive partner at Flagship Pioneering, a builder of breakthrough bioplatform companies. From 2010 to mid-2016 he served as CEO of Novartis Pharmaceuticals, a division of Novartis AG. Previously, David started and led Novartis’ Oncology and Molecular Diagnostic units. Over the course of his career, he led the development and commercialization of over 30 new molecular entities, including major breakthroughs such as Glivec, Tasigna, Gilenya, Cosentyx and Entresto. Mr. Epstein holds a B.S. Degree in Pharmacy from Rutgers University College of Pharmacy and an MBA in Finance and Marketing from the Columbia University Graduate School of Business.

About Roger Dansey, M.D.

Dr. Dansey joined Seagen as CMO in 2018, bringing extensive experience in cancer drug development. Previously, he was Therapeutic Area Head for Late-Stage Oncology at Merck & Co., Inc., where he was responsible for registration efforts for Keytruda (pembrolizumab) across multiple tumor types. Earlier in his career, Dr. Dansey was the Vice President of Oncology Clinical Research at Gilead Sciences and the Global Development Lead for Xgeva (denosumab) at Amgen, where he held multiple roles in oncology and hematology.

Nuvalent Reviews Corporate and Pipeline Achievements and Reports Third Quarter 2022 Financial Results

On November 10, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported recent business and pipeline progress and third quarter 2022 financial results (Press release, Nuvalent, NOV 10, 2022, View Source [SID1234623735]).

"This has been a transformational year for Nuvalent, exemplified by the totality of the data presented at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) which showcased the rapid and meaningful progress our team has made towards our mission of delivering a portfolio of precisely targeted therapies for patients with cancer," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "Importantly, we reported preliminary data from the Phase 1 portion of our ARROS-1 study for NVL-520 in heavily pre-treated patients with ROS1-positive non-small cell lung cancer (NSCLC), representing the first clinical proof-of-concept data from our portfolio. We believe these data support the planned investigation of NVL-520 in the treatment-naïve setting as part of the next phase of our study and continue to support the best-in-class potential of NVL-520 for the treatment of patients with ROS1-positive NSCLC. We look forward to engaging with regulators to discuss the recommended Phase 2 dose and beginning the Phase 2 portion of the ARROS-1 trial."

Dr. Porter continued, "Furthermore, the learnings from our work on NVL-520 and the ARROS-1 trial have directly informed our parallel lead program, NVL-655, and the design of the ALKOVE-1 trial for patients with ALK-positive NSCLC, as well as our earlier-stage pipeline including our third development candidate, NVL-330. Data supporting the differentiated preclinical profiles of NVL-655 and NVL-330 were presented at ENA. Enrollment in the Phase 1 portion of the ALKOVE-1 study continues, and we look forward to updating on each of these programs in the future."

"In just a few years from the company’s creation, we have brought forward three potential best-in-class molecules and delivered clinical proof-of-concept data from our first program, which is a testament to the strength of our team and our ability to execute," added Alexandra Balcom, Chief Financial Officer at Nuvalent. "This execution enabled us to complete an upsized public offering of our common stock that meaningfully extends our expected operating runway and fuels the continued advancement of our clinical-stage pipeline with NVL-520 and NVL-655, as well as our early research and development pipeline, led by NVL-330. With a founding scientific thesis that we have started to see play out in the clinic, this is an energizing time for Nuvalent and we are excited to carry this momentum forward."

Pipeline Progress

Preliminary Dose-Escalation Data from Ongoing ARROS-1 Trial Demonstrates Proof-of-Concept for NVL-520’s Potential Best-in-Class Clinical Profile: Initial data from the Phase 1 dose-escalation portion of Nuvalent’s ongoing ARROS-1 Phase 1/2 clinical trial of NVL-520, its novel, brain-penetrant, ROS1-selective inhibitor, as a potential treatment for patients with advanced ROS1-positive NSCLC and other solid tumors were presented during the "New Drugs on the Horizon" plenary session at ENA 2022. Data presented showed that a favorable preliminary safety profile was observed with NVL-520 treatment with no dose-limiting toxicities, treatment-related serious adverse events, treatment-related dizziness, or adverse events leading to treatment reductions or discontinuations. Additionally, treatment with NVL-520 resulted in encouraging preliminary signs of activity observed across all dose levels in heavily pre-treated patients with ROS1-positive NSCLC, including in subgroups of patients with G2032R resistance mutation or with brain metastases.

The ARROS-1 clinical trial is continuing to enroll patients in the Phase 1 portion of the study and is focused on further characterizing the safety profile of NVL-520, its pharmacokinetic profile, and determining the recommended Phase 2 dose.

New Data in Patient-Derived Models Continues to Support Best-in-Class Preclinical Profile of Parallel Lead Candidate, NVL-655: A poster presented at ENA 2022 included new preclinical data on NVL-655, Nuvalent’s brain penetrant, ALK-selective inhibitor, in additional patient derived models harboring single and compound ALK resistance mutations. Notably, NVL-655 induced regression in an in vivo model derived from a patient with ALK fusion-positive NSCLC harboring G1202R/L1196M compound mutation after disease progression on sequential crizotinib, alectinib and lorlatinib treatment. Among all inhibitors tested, NVL-655 showed the broadest preclinical activity across ALK fusion partners and resistance mutations while maintaining a wide selectivity window over TRKB.

Clinical investigation of NVL-655 is ongoing and enrollment is progressing in the Phase 1 portion of the ALKOVE-1 Phase 1/2 study of NVL-655 for patients with advanced ALK-positive NSCLC and other solid tumors. The Phase 1 portion of the ALKOVE-1 trial is focused on characterizing the safety profile of NVL-655, its pharmacokinetic profile, and determining the recommended Phase 2 dose.

Preclinical Profile of NVL-330 Demonstrates Achievement of Target Characteristics of Potency and Selectivity for HER2 Exon 20 Insertion Mutations, and Brain Penetration: Nuvalent presented preclinical data characterizing its third development candidate, NVL-330, a novel, brain-penetrant HER2-selective tyrosine kinase inhibitor targeting HER2 exon 20 insertion mutations (HER2ex20) during a poster session at ENA 2022. Preclinical data demonstrated that NVL-330 potently inhibited HER2ex20 in cell-based assays and was highly selective for HER2ex20 as opposed to the structurally related wild-type EGFR and other off-target kinases – a critical aspect of NVL-330’s design given that off-target inhibition of EGFR results in dose-limiting side effects including skin rash and gastrointestinal toxicity. In addition, given its demonstrated preclinical brain penetrance and intracranial activity, NVL-330 has the potential to treat or prevent brain metastasis as a potential best-in-class molecule.

Financing Highlight

Completed Upsized Public Offering of Common Stock Raising $264.5 Million in Gross Proceeds: On November 3, 2022, Nuvalent closed an upsized underwritten public offering of 7,895,522 shares of Class A common stock at a price to the public of $33.50 per share. The gross proceeds from the offering were approximately $264.5 million, before deducting underwriting discounts, commissions and other offering expenses, which when combined with the company’s existing cash, cash equivalents and marketable securities as of September 30, 2022, is expected to extend the company’s operating runway into the second half of 2025.

Upcoming Events

Evercore ISI HealthCONx Conference 2022: Management will be participating in a fireside chat during the Evercore ISI HealthCONx Conference 2022 on Wednesday, November 30, 2022, at 8:50 a.m. ET.

The Piper Sandler 34th Annual Healthcare Conference: Management will be participating in a fireside chat during The Piper Sandler 34th Annual Healthcare Conference on Thursday, December 1, 2022, at 9:00 a.m. ET.

Third Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $240.1 million as of September 30, 2022. The company’s cash, cash equivalents and marketable securities as of September 30, 2022, in combination with the proceeds from the follow-on offering, are expected to be sufficient to fund the company’s current operating plan into the second half of 2025.

R&D Expenses: Research and development (R&D) expenses were $14.6 million for the third quarter of 2022.

G&A Expenses: General and administrative (G&A) expenses were $5.8 million for the third quarter of 2022.

Net Loss: Net loss for the third quarter of 2022 was $19.7 million, or $0.41 per share.

Synlogic Reports Third Quarter 2022 Financial Results and Provides Business Update

On November 10, 2022 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage biotechnology company developing medicines for metabolic and immunological diseases through its proprietary approach to synthetic biology, reported financial results for the third quarter ended September 30, 2022 and provided an update on its pipeline programs (Press release, Synlogic, NOV 10, 2022, View Source [SID1234623734]).

"We’re thrilled with the recently announced results of our Phase 2 Synpheny-1 study in phenylketonuria (PKU), which demonstrates the potential to provide a transformative treatment option for patients," said Aoife Brennan, M.B. Ch.B, Synlogic President and Chief Executive Officer. "These data also validate our platform and approach to drug development, and we are looking forward to additional readouts from our programs for homocystinuria (HCU) and enteric hyperoxaluria (EH) later this year."

Anticipated Upcoming Milestones

Initiate the Phase 3 trial for SYNB1934 for PKU in H1 2023 with Phase 3 readiness activities currently underway.

Share data from the Phase 1 trial in healthy volunteers for SYNB1353 for HCU in 2022.

Share proof of concept data for SYNB8802 for EH in 2022.

Recent Business Highlights

Announced positive top-line data from the Phase 2 Synpheny-1 study of SYNB1934 and SYNB1618 in PKU.

Confirmed that SYNB1934 will progress to the Phase 3 registrational study expected to begin in H1 2023.

Earned a research milestone for the achievement of prespecified success criteria under the research collaboration agreement with Roche for the discovery of a novel Synthetic Biotic for the treatment of inflammatory bowel disease (IBD).

Third Quarter 2022 Financial Results

As of September 30, 2022, Synlogic had cash, cash equivalents and short-term investments of $91.7 million.

Revenue for the three months ended September 30, 2022 was $0.7 million compared to $0.9 million for the corresponding period in 2021. Revenue in both periods was associated with the ongoing research collaboration with Roche for the discovery of a novel Synthetic Biotic for the treatment of IBD.

For the three months ended September 30, 2022, Synlogic reported a consolidated net loss of $17.9 million, or $0.25 per share, compared to a consolidated net loss of $16.0 million, or $0.29 per share, for the corresponding period in 2021.

Research and development expenses were $14.6 million for the three months ended September 30, 2022 compared to $13.4 million for the corresponding period in 2021.

General and administrative expenses were $4.4 million for the three months ended September 30, 2022 compared to $3.6 million for the corresponding period in 2021.

Financial Outlook

Based upon its current operating plan and balance sheet as of September 30, 2022, Synlogic expects to have sufficient cash to be able to fund operations into 2024.

CRISPR Therapeutics Presents Data at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting

On November 10, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported data for CTX130 for the treatment of relapsed or refractory renal cell carcinoma (RCC) as an oral presentation delivered by City of Hope’s Sumanta Pal, M.D. Additionally, together with collaborators at the Moffitt Cancer Center, the Company presented preclinical data in a poster presentation demonstrating the potential of potency-enhanced anti-CD83 CAR-T cells in preventing relapse in acute myeloid leukemia (AML) (Press release, CRISPR Therapeutics, NOV 10, 2022, View Source [SID1234623733]).

"We are very pleased by the encouraging data from our first-in-human clinical trial exploring CD70-targeting CAR-T cell therapy in clear cell RCC. In this trial, treatment with CTX130 resulted in a durable complete response, and the trial demonstrated a favorable disease control rate overall. We remain excited by the results presented today for the CTX130 trial for the treatment of relapsed or refractory RCC," said Phuong Khanh (P.K.) Morrow, M.D., FACP, Chief Medical Officer of CRISPR Therapeutics. "Additionally, we presented a poster highlighting preclinical data that demonstrates that CRISPR-edited allogenic anti-CD83 CAR-T cells show potent activity in models of AML and can be a promising CAR-T target for the treatment of AML."

"At present, a treatment that offers patients with advanced kidney cancer the possibility of a durable remission with limited toxicity remains elusive. Our data shared today show encouraging activity for an allogeneic CAR-T therapy in this setting and highlights the potential of this modality for these patients," added Sumanta Pal, M.D., Professor, Department of Medical Oncology and Therapeutics Research, Co-director, Kidney Cancer Program, and medical oncologist at City of Hope, one of the largest cancer research and treatment organizations in the United States.

Key details and takeaways from the oral presentation and poster include:

Title: CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Results from the Phase 1 COBALT-RCC study
Abstract Number and Type: 558, oral presentation
Session Number: 113, Cellular Therapies + Bispecifics
Date and Time: Thursday, November 10, 2022, 5:37 PM ET

This first-in-human clinical trial exploring CD70-targeting CAR-T cell therapy in clear cell RCC (ccRCC) showed a tolerable safety profile with no off-target toxicities and encouraging antitumor activity.
One patient experienced a durable complete response, the first to be achieved with allogeneic CAR-T cell therapy in patients with relapsed/refractory solid tumors.
CTX130 achieved a 77% disease control rate in a heavily pretreated RCC patient population. The longest duration of stable disease achieved was observed for 7.8 months and ongoing at the time of data cutoff. During periods of stable disease, patients did not receive any other anticancer therapies.
The results from the COBALT-RCC study represent a clinically meaningful proof-of-concept for further exploration of CD70-targeting CAR-T cells in ccRCC and other CD70+ malignancies.
A next generation anti-CD70 CAR-T program (CTX131) is being developed, which incorporates the edits in CTX130 with additional edits to the Regnase-1 and TGFBR2 genes. These additional edits have been shown to significantly increase potency of the CAR-T cells in preclinical models.
Title: CRISPR/Cas9 gene-edited, allogeneic anti-CD83 CAR-T cells demonstrate potent activity in GvHD and AML tumor models
Abstract Number and Type: 367, poster
Date and Time: Thursday, November 10, 2022, 9:00 AM – 9:00 PM ET

CD83 is a promising CAR-T target for the treatment of AML.
While anti-CD83 CAR-T cells show encouraging activity alone, that activity can be improved through a variety of means, including knock out of CD83 to prevent CAR-mediated fratricide, knock out of B2M to reduce allogeneic rejection, and combination with belatacept.
CRISPR/Cas9-mediated disruption of Regnase-1 and TGFBR2 expression further improves potency and survival in AML models in vivo.
The presentations are available for viewing at View Source

Phio Announces New Appointments to Leadership Team, Reports on Third Quarter 2022 Financial Results and Provides Business Update

On November 10, 2022 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), reported new appointments to the leadership team, reported its financial results for the quarter ended September 30, 2022 and provided a business update (Press release, Phio Pharmaceuticals, NOV 10, 2022, View Source [SID1234623732]). Phio is a clinical stage biotechnology company whose proprietary INTASYL technology makes immune cells more effective in killing tumor cells. INTASYL is the only self-delivering RNAi technology focused on immuno-oncology therapeutics.

The continuing enrollment in its first-in-human clinical study of PH-762 for advanced melanoma, along with recent positive data from four of its preclinical studies, has attracted new and industry-experienced executives to the Company. The new leadership team will join the current executive team to move the Company forward as it evolves its proprietary platform, INTASYL, from discovery to development.

The newly expanded leadership team is led by industry veteran Robert Bitterman, a member of the board of directors since 2012. Appointed Executive Chairman in September of this year, he assumed the duties leading all aspects of the Company’s operations. Mr. Bitterman brings 25 years of executive leadership experience in the pharmaceutical and biologic life science industry. He also has prior experience in senior financial and investor relations roles.

A key part of this new leadership team includes the appointment of Linda Mahoney as Vice President of Project Development, where she will lead the coordination of a multifunctional team to advance INTASYL compounds through the clinical development process. Ms. Mahoney is a pharmaceutical development executive with more than 25 years of experience in the industry. Previously, Ms. Mahoney was Vice President of Scientific Operations and Business Development at Cutanea Life Sciences, Inc. She also held positions in project management, product development and commercial supply chain at Sanofi-Aventis. Ms. Mahoney led numerous cross-functional pharmaceutical project teams through all stages of development, from product concept through commercialization.

Supporting the leadership team through the clinical development process is Dr. Mary Spellman, a board-certified dermatologist. Dr. Spellman will be working with the Company as a medical advisor and clinical development consultant. Dr. Spellman recently served as Chief Medical Officer at Castle Creek Biosciences, and prior to that at Menlo Therapeutics. She has contributed to the initiation of numerous Investigational New Drug applications, and to multiple drug and biologic marketing applications in a spectrum of clinical indications. Dr. Spellman is a Fellow of the American Academy of Dermatology, and currently is President of the Dermatologists in Industry organization. She is a former Associate Editor and now is a Reviewer for the Journal of the American Academy of Dermatology.

Phio’s business development activities will be supplemented by Michael Cozart, Managing Partner at LifeSci Consulting, LLC, a global strategy, consulting, and transaction advisory firm.

Recent Corporate Updates

Phio’s research partner, Helmholtz Munich, presented preclinical data on Phio’s lead clinical product PH-762, an INTASYL compound targeting PD-1, at the 9th Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (ITOC) annual meeting. PH-762 demonstrated increases in T cell population expressing stem-cell like characteristics. This increase in T cell population is expected to improve T cell persistence in vivo, therefore, resulting in enhanced duration of anti-tumor activity.
At the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), Phio presented four posters demonstrating anti-tumor activity in preclinical models with our INTASYL compounds silencing the proteins BRD4, CTLA4, TIGIT and CTGF. Also, in preparation for an upcoming clinical trial in collaboration with our partner AgonOx, Inc., a poster demonstrating ability to manufacture clinical scale grade TIL with and without PH-762, our INTASYL compound targeting PD-1 was presented. An additional poster reported on the clinical trial design and update on the enrollment in our Phase 1b study of PH-762 for the treatment of advanced melanoma.
Upcoming Pipeline Milestones

Plans to initiate a clinical trial evaluating the use of PH-762 and DP TIL in ACT during the fourth quarter of 2022 in partnership with AgonOx, Inc.
Expects to finalize IND-enabling studies for PH-894 by year end 2022
Expects to report top-line data from the first group of subjects with advanced melanoma in the clinical trial for PH-762 in the first quarter of 2023
Additional data publications on the Company’s pipeline programs
Financial Results

Cash Position

At September 30, 2022, the Company had cash of $14.5 million as compared with $24.1 million at December 31, 2021. The Company expects its current cash will be sufficient to fund currently planned operations for at least the next 12 months.

Research and Development Expenses

Research and development expenses decreased 6% to approximately $2.5 million for the quarter ended September 30, 2022, compared with approximately $2.7 million for the quarter ended September 30, 2021. The decrease in research and development expenses was primarily due manufacturing costs for PH-762 and PH-894 and the preclinical studies required for the Company’s PH-762 intratumoral clinical trial that were incurred in the prior year period offset by increases in research and development expenses for the preclinical studies required for the Company’s planned clinical trial with PH-894 conducted in the current year period.

General and Administrative Expenses

General and administrative expenses were approximately $1.1 million for the quarters ended September 30, 2022 and 2021 and were consistent quarter over quarter.

Net Loss

Net loss decreased 4% to approximately $3.6 million, or $0.26 per share, for the quarter ended September 30, 2022, compared with $3.7 million, or $0.28 per share, for the quarter ended September 30, 2021. The decrease in net loss was primarily attributable to the decrease in research and development expenses as described above.

About INTASYL

INTASYL is the only self-delivering RNAi technology focused on immuno-oncology therapeutics. INTASYL compounds are chemically modified siRNA’s that provide efficient, spontaneous cellular uptake and potent, long lasting intracellular activity targeting a broad range of cell types and tissues. INTASYL drugs precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized formulations or drug delivery systems. In comparison to biologics and cell and gene therapies, INTASYL has a favorable non-clinical toxicity and safety profile, and a streamlined chemical synthesis that reduces costs and offers substantial convenience to the prescriber and patient.

PH-762 is an INTASYL compound that reduces the expression of PD-1, a protein that inhibits T cells’ ability to kill cancer cells. By suppressing PD-1, the T cells are re-activated to kill cancer cells. PH-762 is being developed as a standalone drug therapy (Direct-to-Tumor) and also in combination with adoptive cell therapy. PH-762 is in a Phase 1b study for the treatment of advanced melanoma.

PH-894 is an INTASYL compound that silences BRD4, a protein that controls gene expression in both T cells and tumor cells, thereby effecting the immune system as well as the tumor. What sets this compound apart is its dual mechanism: INTASYL PH-894 suppression of BRD4 in T cells results in T cell activation; additionally, suppression of BRD4 in tumor cells results in tumors becoming more sensitive to T-cell killing.

PH-804 is an INTASYL compound that targets TIGIT, a protein that inhibits the activity of Natural Killer (NK) cells. A recent study demonstrated that NK cells, when treated with PH-804, increased activation and enhanced the ability of NK cells to kill cancer cells.