On November 10, 2022 Aravive, Inc. (Nasdaq: ARAV, "the Company"), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, reported financial results for the third quarter ended September 30, 2022 and provided corporate updates (Press release, Aravive, NOV 10, 2022, View Source [SID1234623740]).

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"Aravive continues to make tremendous progress on all fronts," said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "All development activities around our PROC Phase 3 trial, including patient enrollment and CMC, remain on track to deliver topline data in mid-2023. Our trials in clear cell renal cancer and pancreatic cancer continue to provide encouraging data. Importantly, we have been able to secure the proper funding to advance all programs beyond the PROC readout, allowing us to focus on the critical clinical activities around our trials, particularly the PROC registrational study. In addition to the funding itself, we have added new support from a strong and respected syndicate of leading biotech investors. We are grateful for their confidence in both our science and our ability to move it ahead."

Recent Corporate Highlights

The Company Completes PIPE Offering Adding Funding to Support Operations Beyond PROC Readout
In October, the Company raised approximately $41.5 million in gross proceeds from a private placement offering with new biotechnology investors, existing investors and certain of the Company’s management and directors. This funding, along with the receipt of the Company’s milestone payment (see below), takes our cash runway into late 2023, beyond the readout on our Phase 3 ovarian cancer trial. Pro forma cash at September 30, 2022, giving effect to the capital raise (after transaction expenses), milestone payment and cash balances on that date is approximately $73 million. Current common shares outstanding after the offering are 59,826,881 in addition to 15,870,199 prefunded warrants, for a total of 75,697,080 basic shares outstanding.

Continued Progress with the Company’s Partner in China Results in Milestone Payment
Our partner in China, 3D Medicines enrolled patients into its Phase 3 PROC trial, which begins their Phase 3 clinical activity towards ultimate approval in China. The Company received the $6 million payment related to achievement of this milestone in October.

The Phase 3 Platinum Resistant Ovarian Cancer (PROC) Trial Remains On Track
The registration-directed Phase 3 program of batiraxcept in combination with paclitaxel in PROC remains on track to complete enrollment around year-end 2022. The Company continues to expect to report topline data from the trial by mid-2023. CMC work remains on track with the goal of filing a Biologics License Application (BLA) by year-end 2023. The global, randomized, double-blind, placebo-controlled Phase 3 trial is evaluating efficacy and tolerability of 15 mg/kg batiraxcept in combination with paclitaxel versus placebo in combination with paclitaxel. The trial aims to enroll 350 patients with platinum resistant, high-grade serous ovarian cancer who have received 1-4 prior lines of therapy.

Updated Clear Cell Renal Cell Cancer (ccRCC) Data Continues to Be Encouraging
As of August 8, 2022, 26 previously treated (2L+) patients with ccRCC have been treated with batiraxcept in the Phase 1b portion of a Phase 1b/2 trial at doses of 15 mg/kg (n=16) and 20 mg/kg (n=10), plus cabozantinib 60 mg daily. There were no dose limiting toxicities observed at either dose. The best overall response rate (ORR, confirmed) in the ITT population was 42%. One of the objectives of the ongoing Phase 1b/2 ccRCC trial is to evaluate the correlation of baseline serum soluble AXL (sAXL)/GAS6 (biomarker) with radiographic response in patients with ccRCC treated with batiraxcept plus cabozantinib. The best ORR in the biomarker high population was 55%. The 9-month progression-free survival (PFS) rate was 65% in the ITT population and 72% in the biomarker high population. The Company has discussed a registrational path with the US FDA that includes use of the sAXL/Gas6 ratio as a basis for an accelerated approval.

The open-label Phase 2 portion of the clinical trial initiated January 31, 2022 and is expected to enroll 55 patients across three parts. Part A is expected to enroll approximately 25 patients and investigate 15 mg/kg batiraxcept in combination with cabozantinib in 2L+ ccRCC patients. Part B is expected to enroll approximately 20 patients and evaluate 15 mg/kg batiraxcept in combination with nivolumab and cabozantinib as a potential front-line treatment for ccRCC. Part C is expected to evaluate 15 mg/kg batiraxcept monotherapy in approximately 10 patients with ccRCC who are not eligible for curative intent therapies.

The Company expects to report additional data from the P1b portion and preliminary data from the P2 portion of the ccRCC trial mid-2023.

Expansion of Phase 1b Pancreatic Adenocarcinoma Study
The Company provided an update on the Phase 1b pancreatic study on September 27, 2022 for 18 patients who had been treated with 15 mg/kg batiraxcept (Days 1 & 15) plus nab-paclitaxel (125 mg/m2 on Days 1, 8, & 15) and gemcitabine (1000 mg/m2 on Days 1, 8, & 15) and have pharmacokinetic data. Consistent with other Phase 1b cancer studies with batiraxcept, there is a relationship between batiraxcept exposures and clinical activity such that 5 of 9 patients in the PDAC study whose batiraxcept levels exceeded the minimum efficacious concentration (MEC) of batiraxcept had a response versus 1 of 9 patients in the low MEC group. Similarly, the mPFS in the high MEC group was 5.6 months (95% CI 2.1, not evaluable) versus 2.7 months (95% CI 1.1, 5.4) in the low MEC group. In May 2022, the Company had reported that batiraxcept was generally well-tolerated in combination with gemcitabine and nab-paclitaxel with no unexpected safety signals. Based on these data, the Company intends to dose an additional 6-18 patients at higher doses (20 mg/kg and potentially 25 mg/kg) to see if a higher dose will increase the proportion of patients who will achieve high MEC of batiraxcept and increase the clinical activity of batiraxcept in combination with gemcitabine plus nab-paclitaxel. Preliminary data from the 20 mg/kg cohort is expected in the second half of 2023.
Third Quarter 2022 Financial Results
Revenues for the three months ended September 30, 2022, were approximately $4.9 million, compared to approximately $1.6 million for the three months ended June 30, 2022. Revenues were derived solely from the Company’s collaboration and license agreement with 3D Medicines, executed in November 2020 to develop and commercialize batiraxcept in oncology indications in China. Revenues represent 1) a portion of initial signing and milestone recorded from 3D Medicines that is recognized at the time it is probable the milestone will be met and 2) a portion of the milestone that is deferred and recognized over the PROC trial period. The increase in revenue was driven primarily by the achievement during the third quarter of 2022 of a development milestone from the Company’s licensee, 3D Medicines, based on the initiation of the global Phase 3 PROC clinical trial in China as part of the collaboration and license agreement.

Total operating expenses for the three months ended September 30, 2022, were $21.5 million, compared to $21.0 million for the three months ended June 30, 2022. Research and development expense for the three months ended September 30, 2022, was $18.7 million, compared to $17.3 million for the three months ended June 30, 2022. The increase in research and development expense is primarily attributable to increases in CMC-related costs. General and administrative expense for the three months ended September 30, 2022 was $2.8 million, compared to $3.7 million for the three months ended June 30, 2022. The decrease in general and administrative expense is primarily attributable to decreased stock-based compensation, consulting expense, and severance expense.

Aravive reported a net loss of $15.7 million, or $0.51 per share, for the three months ended September 30, 2022, compared to a net loss of $18.5 million, or $0.61 per share, for the three months ended June 30, 2022.

Cash Position
As of September 30, 2022, cash and cash equivalents were $27.9 million, compared to $46.8 million as of June 30, 2022 and $59.4 million as of December 31, 2021. During October 2022, the Company received a $6 million milestone payment from the Company’s licensee, 3D Medicines, Inc. (recorded as an account receivable on the consolidated balance sheet as of September 30, 2022) and raised approximately $41.5 million in gross proceeds from a private placement offering. The Company believes that its existing cash and cash equivalents will be sufficient to sustain operations into the fourth quarter of 2023.

On November 10, 2022 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported financial results for the third quarter ended September 30, 2022 and provided a corporate update (Press release, Jounce Therapeutics, NOV 10, 2022, View Source [SID1234623739]).

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"We have continued to execute across our pipeline of innovative immunotherapy candidates in the third quarter, especially in the Phase 2 cohorts of the INNATE study. We are proud to be sharing multiple sets of data from our discovery and development programs at two important immuno-oncology conferences this year," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "Our goal is to strive for a meaningful immunotherapy for patients who have few options. This is at the heart of our approach to developing novel mechanisms guided by biomarkers."

Pipeline Update & Highlights:

JTX-8064 (LILRB2/ILT4)

INNATE Phase 1 dose escalation data to be presented at ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress. A poster will be presented on the Phase 1 dose escalation data, including all 31 Phase 1 dose escalation patients, at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Annual Congress 2022 (ESMO-IO) being held from December 7-9 in Geneva, Switzerland. Data presented will include safety, pharmacokinetics, receptor occupancy, and preliminary efficacy data.
Continued to advance INNATE Phase 2 trial across multiple indications. Jounce is evaluating JTX-8064 in the ongoing Phase 2 portion of the INNATE clinical trial, which is comprised of indication specific expansion cohorts, including one monotherapy cohort and initially seven cohorts in combination with pimivalimab (pimi), the Jounce PD-1 inhibitor. Each combination cohort is a Simon’s 2-stage design, enrolling 10 patients for an initial assessment of response, and then enrolling to a total of 29 patients if prespecified response criteria are met. Today, Jounce is announcing that enrollment of the first 10 patients has been completed in all 7 phase 2 combination cohorts. Updates on the status of combination cohorts include: 1) Stage 1 criteria met for PD-1 or PD-L1 (PD-(L)1) inhibitor resistant 2L/3L head and neck squamous cell carcinoma (HNSCC), currently under review for expansion, 2) Stage 1 criteria not met for PD-(L)1 inhibitor naïve sarcoma, 3) Two combination cohorts, in 1L PD-(L)1 inhibitor naïve HNSCC and PD-(L)1 inhibitor resistant cutaneous squamous cell carcinoma, along with the ovarian monotherapy cohort, still have the potential to meet criteria to advance from Stage 1 to Stage 2. Jounce also announces that enrollment has started in a new combination cohort in PD-(L)1 inhibitor resistant 2L/3L biliary tract cancer (BTC), informed by a confirmed durable response in Phase 1 in combination with pimi. In the Phase 2 cohorts that had previously met the criteria to expand, the ovarian cohort has over-enrolled with 35 patients, and the renal cell cohort is nearing complete enrollment with 26 of 29 patients enrolled.
Jounce now expects to be in position to share additional results from the phase 2 portion of the study in the first half of 2023, instead of ESMO (Free ESMO Whitepaper)-IO in December 2022. In the preliminary data in over 80 patients across all combination cohorts, Jounce believes it has seen signs of clinical activity of JTX-8064 but not broad activity leading to rapid proof-of-concept (POC). Efficacy data is taking time to mature, and assessment of whether POC will be achieved, based on confirmed responses in each fully expanded cohort, will enable the presentation of a complete and interpretable data set. Both the JTX-8064 monotherapy and pimi combination continue to demonstrate an acceptable safety profile to date.
Vopratelimab (ICOS) and Pimivalimab (PD-1)

SELECT Phase 2 data to be presented at ESMO (Free ESMO Whitepaper)-IO Annual Congress 2022. Jounce will present the SELECT data in a poster at ESMO (Free ESMO Whitepaper)-IO. SELECT is a randomized Phase 2 trial evaluating vopratelimab (vopra), Jounce’s inducible T cell costimulator (ICOS) agonist, in combination with pimi versus pimi alone in immunotherapy naïve, TISvopra biomarker-selected, second line non-small cell lung cancer patients. The poster will update previously announced data on primary and secondary endpoints based on a longer duration of follow up. As previously reported, vopra 0.03 mg/kg in combination with pimi resulted in a 40% response rate and an 80% six month landmark progression-free survival (PFS) by independent central radiology review. These continue to compare favorably to updated results for pimi monotherapy, with a 27.8% response rate and 36% six month landmark PFS, as will be reported at ESMO (Free ESMO Whitepaper)-IO. Jounce plans to pursue a partnership to enable further development of vopra 0.03 mg/kg in combination with a PD-1 inhibitor.
JTX-1484 (LILRB4/ILT3)

Continued advancement of JTX-1484. JTX-1484 is a monoclonal antibody with an emerging differentiated profile designed to block human LILRB4 (ILT3) expressed on myeloid cells in the tumor microenvironment with the potential to reduce immune suppression and enhance T cell functionality. JTX-1484 is currently in investigational new drug (IND) enabling activities, with the goal of filing an IND application in 2023.
JTX-1484 preclinical poster presentation at SITC (Free SITC Whitepaper). Jounce will be presenting a preclinical poster today on JTX-1484 at this year’s annual Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) meeting being held from November 9-11 in Boston, MA. The poster will highlight the preclinical evaluation of JTX-1484, an anti-LILRB4 antagonist antibody, for re-programming of immunosuppressive myeloid cells.
Discovery Pipeline

LILRB family preclinical data poster presentation at SITC (Free SITC Whitepaper). Jounce will present preclinical data in a poster at the SITC (Free SITC Whitepaper) annual meeting today on the LILRB family of receptors and the characterization of the expression and function of LILRB receptors on human immune cells in tumor and blood samples across different cancer types.
Productive discovery engine. Jounce continues to advance its growing immuno-oncology pipeline. Its discovery engine is built upon the capability to thoroughly interrogate different cell types in the tumor microenvironment, including T cells and myeloid cells. This approach has resulted in four clinical stage programs, with a fifth in IND enabling studies, over the last 6 years.
Business Update

Jounce earns clinical milestone under the CCR8 exclusive license agreement with Gilead Sciences, Inc. A $15.0 million clinical milestone payment from Gilead Sciences, Inc. (Gilead) was earned in October 2022, under the exclusive license agreement for GS-1811, an anti-CCR8 antibody for which Gilead has exclusive rights to develop and commercialize. To date, Jounce has earned $40.0 million of the $685.0 million in development, regulatory, and commercial milestones possible under the agreement. Additionally, Jounce will be eligible to receive royalties ranging from high single digit to mid-teens based upon on any future worldwide product sales of GS-1811.
Third Quarter 2022 Financial Results:

Cash position: As of September 30, 2022, cash, cash equivalents and investments decreased to $130.3 million, compared to $220.2 million as of December 31, 2021. The decrease was due to operating expenses incurred during the period.
License and collaboration revenue: Jounce did not recognize any revenue during the third quarter of 2022 or 2021. The $15.0 million milestone earned under the Gilead license agreement in October is expected to be received in the fourth quarter of 2022.
Research and development expenses: Research and development expenses were $23.8 million for the third quarter of 2022, compared to $23.3 million for the same period in 2021. The increase in R&D expenses was due to increased manufacturing activities and lab supply purchases to support research activities, partially offset by decreased external clinical and regulatory costs for our vopratelimab development program.
General and administrative expenses: General and administrative expenses were $7.7 million for the third quarter of 2022, compared to $6.9 million for the same period in 2021. The increase in G&A expense was attributable to increased compensation costs due to increased headcount.
Net loss: Net loss was $31.0 million for the third quarter of 2022, resulting in basic and diluted net loss per share of $0.60. Net loss was $30.1 million for the same period in 2021, resulting in a basic and diluted net loss per share of $0.59. The increase in net loss is attributable to increased operating expenses in the third quarter of 2022 as compared to 2021.
Financial Guidance:

Based on its current operating and development plans and cost containment efforts, Jounce is reiterating its financial guidance for 2022. Gross cash burn on operating expenses and capital expenditures for the full year 2022 is expected to be at the lower end of the range of $115.0 million to $130.0 million. Jounce expects its existing cash, cash equivalents and investments to be sufficient to enable the funding of its operating expenses and capital expenditure requirements into the first quarter of 2024.

Conference Call and Webcast Information:

Jounce Therapeutics will host a live conference call and webcast today at 8:00 a.m. ET. To access the conference call, participants may register here.1 It is advised to register at least 10 minutes prior to joining the call. The live webcast can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.jouncetx.com. The webcast will be archived and made available for replay on the company’s website approximately two hours after the call and will be available for 30 days thereafter.

On November 10, 2022 BeiGene, (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology, reported BRUKINSA (zanubrutinib) has been approved in Brazil for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) and adult patients with relapsed/refractory (R/R) marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (Press release, BeiGene, NOV 10, 2022, View Source [SID1234623738]). BRUKINSA was previously approved as a treatment in Brazil for adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. BeiGene is focused on developing innovative and affordable oncology medicines to improve treatment outcomes and access for patients worldwide.

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"We have carried out an expansive and global clinical development program for our innovative BTK inhibitor, BRUKINSA, which has led to approval for the treatment of WM, MZL, and MCL in Brazil. These approvals demonstrate our commitment to accelerate development and broaden access to innovative medicines around the globe," said Alex Carvalho, Country General Manager, Brazil, at BeiGene. "I’m proud to bring this potentially best-in-class medicine to Brazil and look forward to working with our partner, Adium on commercialization activities."

About BRUKINSA

BRUKINSA (zanubrutinib) is a small-molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. BRUKINSA was specifically designed to deliver targeted and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.

BRUKINSA is supported by a broad clinical program which includes more than 4,700 subjects in 35 trials in more than 25 countries and regions. To date, BRUKINSA is approved in 58 markets, including the United States, China, the European Union Great Britain, Canada, Australia, South Korea, Switzerland and additional international markets.

BeiGene Oncology

BeiGene is committed to advancing best- and first-in-class clinical candidates internally or with like-minded partners to develop impactful and affordable medicines for patients across the globe. We have a growing R&D and medical affairs team of more than 3,500 colleagues dedicated to advancing more than 100 clinical trials that have involved more than 20,000 subjects. Our expansive portfolio is directed predominantly by our internal colleagues supporting clinical trials in more than 45 countries and regions. Hematology-oncology, and solid tumor targeted therapies, and immuno-oncology are key focus areas for the Company, with both monotherapies and combination therapies prioritized in our research and development. BeiGene currently has three licensed medicines discovered and developed in our own labs: BTK inhibitor BRUKINSA in the U.S., China, the European Union, Great Britain, Canada, Australia, South Korea, Switzerland, and additional international markets; and the non-FC-gamma receptor binding anti-PD-1 antibody tislelizumab as well as the poly adenosine diphosphate-ribose polymerase (PARP) inhibitor pamiparib in China.

BeiGene also partners with innovative companies who share our goal of developing therapies to address global health needs. We commercialize a range of oncology medicines in China licensed from Amgen, Bristol Myers Squibb, EUSA Pharma, and Bio-Thera. We also plan to address greater areas of unmet need globally through our other collaborations including Mirati Therapeutics, Seagen, and Zymeworks.

In January 2021 BeiGene and Novartis announced a collaboration granting Novartis rights to co-develop, manufacture, and commercialize BeiGene’s anti-PD-1 antibody tislelizumab in North America, Europe, and Japan. Building upon this productive collaboration, BeiGene and Novartis announced an option, collaboration, and license agreement in December 2021 for BeiGene’s TIGIT inhibitor ociperlimab that is in Phase 3 development. Novartis and BeiGene also entered into a strategic commercial agreement through which BeiGene will promote five approved Novartis oncology products across designated regions of China.

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.

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]).

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"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.