A2 BIOTHERAPEUTICS EMERGES FROM STEALTH MODE WITH $57M SERIES A TO DEVELOP A PIPELINE OF SELECTIVE TUMOR CELL THERAPEUTICS

On November 5, 2019 A2 Biotherapeutics (www.a2bio.com), a biotechnology company developing innovative cell therapies for cancer patients, reported its official launch (Press release, A2 Biotherapeutics, NOV 5, 2019, View Source [SID1234550323]). The company, founded in 2018 by veteran biotechnology leaders, has a unique and potentially broad solution for the central problem of cancer research – targeted killing of tumor cells vs. normal cells. A2 Biotherapeutics employs a powerful discovery and optimization technology to identify antibody and T-cell receptor fragments that bind to targets that are technically challenging but definitively distinguish tumor cells. The target binder platform is seamlessly combined with proprietary cell engineering, modular vector designs, and novel quantitative assays to extend the reach of cell therapies into solid tumors.

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Investors in the $57 million Series A financing include The Column Group, Vida Ventures, Samsara BioCapital and Nextech Invest.

Tumor cells exhibit only subtle differences from normal cells, making it challenging to create cancer therapies that recognize and kill only tumor cells. A2 Biotherapeutics is overcoming this challenge, having already demonstrated targeted killing of tumor cells in its research. The company aims to beat cancer via tumor-specific targeting using a novel approach that considers targets gained or lost in cancer cells. "This approach has the promise of being utilized for multiple tumor types, providing solutions for many cancer patients. A2 Biotherapeutics has potent, highly selective binders that we combine into molecular constructs to integrate multiple signals and potentially provide a large therapeutic window," said Alexander Kamb, Co-Founder and chief scientific officer. Kamb was formerly SVP of Research at Amgen.

To unequivocally distinguish tumor cells from healthy cells, A2 Biotherapeutics is pursuing two target classes. First, the company addresses peptide MHC targets, which are generated inside the cell and presented on the cell surface, providing the potential to access intracellular targets gained in tumors (e.g., neo-antigens). The second target class is tackled through modular cell engineering to deploy a more powerful version of the mechanism used by natural killer cells. This latter approach addresses targets that are irreversibly lost in tumor cells via loss of heterozygosity.

To advance its product candidates, A2 Biotherapeutics has a fully integrated discovery, development and manufacturing organization in Agoura Hills, California with a team that already includes more than 40 staff. Efforts are led by an experienced management team aggregating the experience of ex-Amgen and ex-Kite Pharma drug and cell therapy developers. Scott Foraker, an executive with 25 years of experience at Amgen, was recently hired as president and chief executive officer. "Our unique approach to targeted killing of tumor cells has the potential to create breakthrough cancer therapies that we look forward to bringing to patients, particularly those in need of new approaches," said Foraker.

The company also has the support of distinguished academic experts in cell therapy and T-cell biology, including:

Mark Davis, PhD, Director, Stanford Institute for Immunity, Transplantation and Infection and The Burt And Marion Avery Family Professor of Microbiology and Immunology at Stanford University

Robert Schreiber, PhD, AM Bursky & JM Bursky Distinguished Professor of Pathology & Immunology at the Washington University School of Medicine in St. Louis

David Maloney, MD, PhD, Medical Director of Cellular Immunotherapy at the Immunotherapy Integrated Research Center (IIRC) and Leonard and Norma Klorfine Endowed Chair for Clinical Research at Fred Hutch

George Tsokos, MD, Professor of Medicine at the Harvard Medical School and Chief of Rheumatology at the Beth Israel Deaconess Medical Center in Boston

A2 Biotherapeutics currently has four programs in development with the first clinical candidate expected next year and is open to collaborations to rapidly advance these programs. The company’s plans also include innovations in manufacturing; it will launch an autologous cell manufacturing facility in 2020 with technology scalable for commercial launch. "A2 Biotherapeutics aspires to increase speed to patients and reduce cost of goods by leveraging its cell therapy manufacturing expertise and advances in technology," said Madhu Balachandran, former EVP of Operations at Amgen and member of A2 Biotherapeutics Board of Directors.

Regeneron Reports Third Quarter 2019 Financial and Operating Results

On November 5, 2019 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the third quarter of 2019 and provided a business update (Press release, Regeneron, NOV 5, 2019, View Source [SID1234550339]).

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"Regeneron delivered positive financial and operational results this quarter, marked by significant EYLEA and Dupixent sales growth and progress across our pipeline," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "We are broadening our efforts in retinal and type 2 inflammatory diseases, including initiating late-stage trials of Dupixent in additional type 2 diseases in the coming months. Oncology is a major focus of our research and development efforts, and we are advancing important new potential treatments for patients with a variety of cancers. We currently have six bispecific antibodies in the clinic, and multiple pivotal trials with Libtayo in non-small cell lung, skin, and other cancers."

"This quarter, we realized improving profitability from the Sanofi antibody collaboration, which is contributing to a more diverse earnings base for the Company," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "Our financial results, strength of our balance sheet, and confidence in our business longer-term allow us to continue deploying capital by investing in internal and external innovation to expand our pipeline, while also returning cash to shareholders with the initiation of a $1 billion share repurchase program."

Key Pipeline Progress
Regeneron has 24 product candidates in clinical development, including five of the Company’s U.S. Food and Drug Administration (FDA) approved products for which it is investigating additional indications. Updates from the clinical pipeline include:
EYLEA (aflibercept) Injection

In August 2019, the FDA approved the EYLEA pre-filled syringe, which is expected to be launched before the end of this year.

A Phase 2 study exploring less frequent dosing intervals using a high-dose formulation of aflibercept in wet AMD was initiated.

A Phase 3 study in retinopathy of prematurity was initiated.

Dupixent (dupilumab)

In August 2019, the European Commission (EC) extended its approval of Dupixent in the European Union to include adolescents 12 to 17 years of age with moderate-to-severe atopic dermatitis who are candidates for systemic therapy.

In August 2019, the Company and Sanofi announced that the Phase 3 trial to treat severe atopic dermatitis in children 6 to 11 years of age met its primary and secondary endpoints. Submissions for a supplemental Biologics License Application (sBLA) and Marketing Authorization Application (MAA) for this expanded atopic dermatitis indication in pediatric patients are expected by the end of the year.

In October 2019, the EC approved Dupixent in chronic rhinosinusitis with nasal polyposis (CRSwNP).

The Company and Sanofi plan to initiate Phase 3 studies in bullous pemphigoid, prurigo nodularis, chronic spontaneous urticaria, and additional type 2 inflammatory diseases.

Praluent (alirocumab)

In August 2019, the Company and Sanofi announced the U.S. District Court for the District of Delaware ruled in their favor and found as a matter of law that Amgen’s asserted patent claims for antibodies targeting PCSK9 are invalid based on lack of enablement.

Evinacumab, an antibody to ANGPTL3

In August 2019, the Company announced positive top-line results from a Phase 3 trial of evinacumab in patients with homozygous familial hypercholesterolemia (HoFH). The Company plans to submit a BLA in mid-2020.

REGN-EB3, a multi-antibody therapy to Ebola virus infection

In August 2019, the Company announced that a randomized, controlled trial evaluating four investigational therapies for Ebola virus infection was stopped early because REGN-EB3 was superior to ZMapp (the control arm of the trial since it was considered standard-of-care) in preventing death. REGN-EB3 and another investigational drug are being further studied as part of the Extension Phase of this trial.

The FDA granted Breakthrough Therapy designation for the treatment of Ebola virus infection and the Company has initiated a rolling BLA submission.

REGN5678, a bispecific antibody targeting PSMA and CD28

A Phase 1 study evaluating this first-in-class co-stimulatory bispecific antibody was initiated in prostate cancer.

REGN5093, a bispecific antibody targeting two distinct MET epitopes

A Phase 1 study evaluating this first-in-class bispecific antibody was initiated in MET-altered advanced non-small cell lung cancer.

Share Repurchase Program
In November 2019, the Company’s board of directors authorized a share repurchase program to repurchase up to $1.0 billion of the Company’s Common Stock. Repurchases may be made from time to time at management’s discretion through a variety of methods. The program has no time limit and can be discontinued at any time. No shares have been repurchased under the program to date.

Third Quarter 2019 Financial Results

Total Revenues: Total revenues increased by 23% to $2.048 billion in the third quarter of 2019, compared to $1.663 billion in the third quarter of 2018.

Net product sales were $1.238 billion in the third quarter of 2019, compared to $1.025 billion in the third quarter of 2018. EYLEA net product sales in the United States were $1.188 billion in the third quarter of 2019, compared to $1.022 billion in the third quarter of 2018. Overall distributor inventory levels for EYLEA in the United States remained within the Company’s one-to-two-week targeted range.

Total revenues also include Sanofi and Bayer collaboration revenues(5) of $707 million in the third quarter of 2019, compared to $521 million in the third quarter of 2018. Sanofi collaboration revenue in the third quarter of 2019 included the Company’s share of profits from collaboration antibodies (Dupixent, Praluent, and Kevzara) of $94 million, while Sanofi collaboration revenue in the third quarter of 2018 included the Company’s share of losses from collaboration antibodies of $39 million. The increase in the Company’s share of profits from collaboration antibodies was primarily driven by higher Dupixent profits.

Refer to Table 4 for a summary of collaboration and other revenue.

Research and Development (R&D) Expenses: GAAP R&D expenses were $663 million in the third quarter of 2019, compared to $557 million in the third quarter of 2018. The higher R&D expenses in the third quarter of 2019 were principally due to additional costs incurred in connection with fasinumab as well as our earlier-stage pipeline, and higher headcount and

headcount-related costs. In each of the third quarters of 2019 and 2018, R&D-related non-cash share-based compensation expense was $60 million.

Selling, General, and Administrative (SG&A) Expenses: GAAP SG&A expenses were $420 million in the third quarter of 2019, compared to $369 million in the third quarter of 2018. The higher SG&A expenses in the third quarter of 2019 were primarily due to higher headcount and related costs, as well as an increase in commercialization-related expenses for Dupixent and EYLEA. In the third quarter of 2019, SG&A-related non-cash share-based compensation expense was $41 million, compared to $43 million in the third quarter of 2018.

Cost of Goods Sold (COGS): GAAP COGS was $116 million in the third quarter of 2019, compared to $31 million in the third quarter of 2018. The increase in COGS was primarily due to the Company’s obligation to pay Sanofi its share of Libtayo U.S. gross profits, higher period costs at the Company’s Limerick manufacturing facility, and higher inventory reserves and write-offs.

Income Taxes: In the third quarter of 2019, GAAP income tax expense was $99 million and the effective tax rate was 12.9%, compared to $41 million and 6.5%, respectively, in the third quarter of 2018. The effective tax rate for the third quarter of 2019 was positively impacted, compared to the U.S. federal statutory rate, primarily by federal tax credits for research activities and the foreign-derived intangible income deduction, partly offset by the taxation of certain global intangible low-taxed income. The Company’s effective tax rate for the third quarter of 2018 was positively impacted, compared to the U.S. federal statutory rate, primarily by the tax benefit associated with the U.S. Tax Reform Act and the federal tax credit for research activities.

GAAP and Non-GAAP Net Income(1): GAAP net income was $670 million, or $5.86 per diluted share, in the third quarter of 2019, compared to GAAP net income of $595 million, or $5.17 per diluted share, in the third quarter of 2018.

Non-GAAP net income was $762 million, or $6.67 per diluted share, in the third quarter of 2019, compared to non-GAAP net income of $675 million, or $5.87 per diluted share, in the third quarter of 2018.

A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

This press release uses non-GAAP net income, non-GAAP net income per share, non-GAAP unreimbursed R&D, and non-GAAP SG&A, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles (GAAP). These non-GAAP financial measures are computed by excluding certain non-cash and other items from the related GAAP financial measure. Non-GAAP adjustments also include the estimated income tax effect of reconciling items.

The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company’s control (such as the Company’s stock price on the dates share-based grants are issued or changes in the fair value of the Company’s equity investments) or items that are not associated with normal, recurring operations. Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company’s core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company’s non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by Regeneron should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP. A reconciliation of the Company’s historical GAAP to non-GAAP results is included in Table 3 of this press release.

The Company’s 2019 financial guidance does not assume the completion of any significant business development transactions not completed as of the date of this press release.

A reconciliation of full year 2019 non-GAAP to GAAP financial guidance is included below:

Unreimbursed R&D represents GAAP R&D expenses reduced by GAAP R&D expense reimbursements from the Company’s collaborators and/or customers (refer to Table 4).

The Company’s collaborators provide it with estimates of the collaborators’ respective sales and the Company’s share of the profits or losses from commercialization of products for the most recent fiscal quarter. The Company’s estimates for such quarter are reconciled to actual results in the subsequent fiscal quarter, and the Company’s share of the profit or loss is adjusted on a prospective basis accordingly, if necessary.

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its third quarter 2019 financial and operating results on Tuesday, November 5, 2019, at 8:30 AM. To access this call, dial (800) 708-4540 (U.S.) or (847) 619-6397 (International). A link to the webcast may be accessed from the "Investors and Media" page of Regeneron’s website at www.regeneron.com. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days.

Oncternal Therapeutics Announces Interim Clinical Data on TK216 in Ewing Sarcoma to Be Presented at the CTOS 2019 Annual Meeting

On November 5, 2019 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported that interim data on TK216 – an investigational targeted small molecule inhibitor of ETS transcription factor oncoproteins – will be presented at the Connective Tissue Oncology Society (CTOS) 2019 Annual Meeting in Tokyo, Japan, on November 16, 2019 (Press release, Oncternal Therapeutics, NOV 5, 2019, View Source [SID1234550355]). The oral presentation (abstract 3250355) titled "A Phase 1 Dose Escalation Study of Intravenous TK216 in Patients with Relapsed or Refractory Ewing Sarcoma" will be given by Paul A. Meyers, M.D., Chief, Pediatric Sarcoma Service and Vice Chair for Clinical Affairs of Memorial Sloan Kettering Cancer Center.

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About TK216

TK216 is an investigational, potentially first-in-class small molecule that is designed to inhibit the biological activity of E26 transformation-specific (ETS) transcription factor oncoproteins, including fusion proteins. Tumorigenic gene fusions involving ETS factors are frequently found in tumors such as Ewing sarcoma and prostate cancer, and ETS factors are often overexpressed in many other tumors, including prostate cancer and acute myeloid leukemia (AML). TK216 was developed based on discoveries of Jeffrey Toretsky, M.D., and his team at Georgetown University, who discovered inhibitors of EWS-FLI1 using a novel chemical screening assay. In preclinical models, TK216 binds to EWS-FLI1 and blocks the interaction between ETS family members and RNA helicase A leading to tumor cell apoptosis.

About the Study

TK216 is being evaluated in a Phase 1 clinical study as a single agent and in combination with vincristine in patients with relapsed or refractory Ewing sarcoma, a rare pediatric cancer that has historically been very challenging to treat effectively, particularly for recurrent and metastatic disease. A dose-finding arm of this study is nearing completion, after which Oncternal intends to begin enrolling patients in an expansion cohort of the study to evaluate the clinical response of treatment with TK216 in combination with vincristine, an approved chemotherapy agent. This multi-center study is actively enrolling patients at six clinical trial centers across the U.S. Additional information about the TK216 study may be accessed at ClinicalTrials.gov (NCT02657005).

Precision for Medicine and Akoya Partner to Develop Advanced Liquid Biopsy and Tissue Biomarker Tests

On November 5, 2019 Akoya Biosciences, The Spatial Biology Company reported a strategic alliance with Precision for Medicine (formerly ApoCell), a pioneer in customized biomarker solutions, to develop proprietary liquid biopsy and tissue biomarker tests using Akoya’s Vectra Polaris System (Press release, Akoya Biosciences, NOV 5, 2019, View Source [SID1234550371]). By combining the Vectra Polaris system with Precision for Medicine’s ApoStream technology, the collaboration is designed to advance immuno-oncology candidates in clinical trials using both tumor biopsies and liquid biopsies to generate data required for assessing drug efficacy and validation of companion diagnostics (CDx).

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"We are very excited to be the first commercial laboratory to launch the Vectra Polaris system for image analysis of circulating tumor cells following ApoStream’s isolation and enrichment functionality," said Darren Davis, PhD, Precision for Medicine Senior Vice President. "Together, these technologies will enable accelerated drug development through detection of biomarkers in liquid biopsies. These tools have enabled our scientists to better understand the biological correlation of circulating metastatic cancer cells with cancer cells present in the tumor tissue."

Circulating tumor cells (CTCs) have long been known to exist in cancer patients’ blood. However, the promise of clinical application of CTCs as a liquid biopsy has not born fruit because these cells are difficult to detect using current molecular biology techniques. Precision for Medicine’s proprietary ApoStream technology captures significant quantities of rare circulating cancer cells from whole blood for characterization using Akoya’s Opal technology and Vectra Polaris imaging platform. ApoStream has been used in more than 80 clinical trials, including several ongoing phase III studies for CDx development.

Akoya’s Vectra Polaris Automated Quantitative Pathology System, part of the company’s Phenoptics 2.0 next-generation biomarker multiplexing platform, enables researchers to gain a deeper level of understanding of disease mechanisms related to new cancer immunotherapy approaches. The Vectra Polaris system integrates high throughput, seven-color multispectral imaging with whole-slide scanning in a simplified digital pathology workflow to support the quantification and analysis of tissue sections discernible with Opal detection kits. A recent meta-analysis of several studies showed that incorporating spatial information using Akoya’s multiplexed immunofluorescence technology is important for improving the predictive accuracy of immuno-oncology biomarkers.

The Phenoptics portfolio is capable of interrogating multiple protein markers on any tissue or cytology slide preparation. Precision for Medicine has validated several immune biomarker panels across various therapeutic applications using both types of preparation. These immune panels are currently being used to monitor immune cell infiltration including cancer, psoriasis, lupus and atomic dermatitis.

"The Vectra Polaris imaging system offers an innovative approach to assessing immunotherapy candidates in translational and clinical research," said Dr. Cliff Hoyt, Akoya Vice President of Translational and Scientific Affairs. "We are pleased to see this technology paired with ApoStream for a comprehensive method of imaging CTCs and improving our understanding of disease mechanisms in cancer."

Arena Pharmaceuticals to Present at Upcoming Investor Conferences

On November 5, 2019 Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) reported that members of its senior management team will present at the upcoming investor conferences (Press release, Arena Pharmaceuticals, NOV 5, 2019, View Source [SID1234550504]):

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Credit Suisse 28th Annual Healthcare Conference – Presenting on Tuesday, November 12, at 10:00 AM ET (8:00 AM MT)
Guggenheim Healthcare Talks | Idea Forum | Neuro/Immunology Day – Presenting on Monday, November 18, at 1:45 PM ET
A live audio webcast of each presentation will be available under the investor relations section of Arena’s website at www.arenapharm.com. A replay of each presentation will be available for 30 days following the event.