On December 9, 2019 Transgene (Paris:TNG) reported that Management will participate in the upcoming investor events set out below (Press release, Transgene, DEC 9, 2019, View Source [SID1234552144]).

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Transgene will meet institutional investors at the LifeSci Advisors Corporate Access Event from January 13 to 16, 2020, in San Francisco, USA, concurrent with the J.P. Morgan Healthcare conference.

The Company will also attend:

Oddo Forum: January 9 & 10, 2020 – Lyon, France
Biomed Event: January 28, 2020 – Paris, France

On December 9, 2019 Nektar Therapeutics (NASDAQ: NKTR) reported three presentations at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition for its IL-15 agonist and investigational candidate, NKTR-255 (Press release, Nektar Therapeutics, DEC 9, 2019, View Source [SID1234552160]). Data were presented from a number of preclinical studies conducted in collaboration with researchers from the Dana-Farber Cancer Institute and the Fred Hutchinson Cancer Research Center.

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NKTR-255 is an interleukin-15 (IL-15) receptor agonist, which is currently being evaluated in a Phase 1 clinical study in patients with multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL). NKTR-255 is designed to work by selectively targeting the IL-15 pathway to expand both natural killer (NK) cells and memory CD8 T cell populations.

"The preclinical data being recognized at ASH (Free ASH Whitepaper) demonstrate NKTR-255’s promise in hematological malignancies through its potential to restore both NK cell and memory CD8 T cell compartments in patients," said Loui Madakamutil, Ph.D., Senior Vice President and Head of Discovery and Research at Nektar Therapeutics. "In studies presented by the laboratory of Dr. Nikhil Munshi at Dana-Farber, NKTR-255 enhanced the number and function of NK and CD8+ effector memory T cell populations in peripheral blood and bone marrow from patients with multiple myeloma and, also increased expression of activating receptors found on those NK cells. Separately, researchers from the laboratory of Dr. Cameron Turtle at Fred Hutchinson demonstrated NKTR-255 prevented tumor growth and increased survival of CAR T cells when added to a CD19-targeted CAR T cell regimen in models of B cell lymphoma. This preclinical data reinforces the basis of our ongoing clinical trial evaluating the potential of NKTR-255 in patients with multiple myeloma and non-Hodgkin’s lymphoma."

Details of the preclinical data presentations at ASH (Free ASH Whitepaper) are as follows and are available on the scientific section of Nektar’s website at View Source

Abstract 2866: "Combination of NKTR-255, a polymer conjugated human IL-15, with CD19 CAR T cell immunotherapy in a preclinical lymphoma model," Chou, C., et al. (This study was conducted in collaboration with the Turtle Laboratory in the Fred Hutchinson Cancer Research Center.)

Session: 625. Lymphoma: Pre-Clinical – Chemotherapy and Biologic Agents: Poster II
Date: Sunday, December 8, 2019, 6:00 p.m. – 8:00 p.m. Eastern Standard Time
CAR T cells treated with NKTR-255 demonstrate increased proliferation and survival both in vitro and in vivo which may in part be due to increased expression of bcl-2.
Tumor bearing mice treated with NKTR-255 and CAR T cells have decreased tumor burden and increased survival compared to mice treated with CAR T cells alone.
Tumor-bearing mice previously treated with NKTR-255 and CAR T cells are able to reject tumor re-challenge supporting persistence of functional CAR T cells.
Abstract 4398: "Restoring innate and adaptive immune repertoire in multiple myeloma for therapeutic application," Fernandez, R., et al. (This study was conducted in collaboration with Dr. Nikhil C. Munshi at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute.)
Note: Dr. Rafael Fernandez was recognized with a 2019 ASH (Free ASH Whitepaper) Abstract Achievement Award for this abstract.

Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, Excluding Therapy: Poster III
Date: Monday, December 9, 2019, 6:00 p.m. – 8:00 pm. Eastern Standard Time
Multiple myeloma patients are known to experience impaired innate immunity and a decline in function of NK cells along with lower expression of activating receptors found on these cells.
Treatment with NKTR-255 enhanced the number and function of both NK and CD8+ effector memory T cell populations in peripheral blood from healthy donors and MM patients in a dose dependent manner.
NKTR-255 was also able to revert the inhibitory status of NK cells from MM patients and showed synergy with daratumumab and elotuzumab to significantly increase status of NK susceptibility of the MM cells.
Findings suggest NKTR-255 delivers a significant impact on the activation of effector cell function to efficiently target MM cells.
Details of the Trials in Progress poster presentation are as follows:

Abstract 4459: "A Phase 1, Open-Label, Multi-Center, Dose Escalation and Dose Expansion Study of NKTR-255 As a Single Agent in Relapsed or Refractory Hematologic Malignancies and in Combination with Daratumumab As a Salvage Regimen for Multiple Myeloma," Shah, N., et al.

Session: 704. Immunotherapies: Poster III
Date: Monday, December 9, 2019; 6:00 p.m. – 8:00 p.m. Eastern Standard Time
About the Phase 1 Study of NKTR-255 (NCT04136756)

NKTR-255 is currently being evaluated in an open-label Phase 1, dose escalation and dose expansion study in patients with select hematological malignancies (relapsed or refractory NHL or MM). The dose escalation phase of the study will evaluate the safety and tolerability of NKTR-255 as monotherapy in approximately 40 patients in order to establish a recommended Phase 2 dose (RP2D) for NKTR-255. The dose expansion phase of the study will enroll patients with MM or NHL (relapsed/refractory salvage) to evaluate the NKTR-255 RP2D in combination with targeted antibodies, including anti-CD38 monoclonal antibody, daratumumab in MM and anti-CD20 monoclonal antibody, rituximab in NHL. These studies are designed to assess pharmacokinetic and pharmacodynamic effects, anti-tumor activity and a range of biomarker assessments associated with NK and memory T cell populations.

About NKTR-255

NKTR-255 is an IL-15 receptor agonist designed to activate the IL-15 pathway and expand NK cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances functional NK cell repopulation and formation of long-term immunological memory, which may lead to sustained anti-tumor immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15 and other IL-15 agonists, which are rapidly cleared from the body and have shown diminishing response to successive doses.1 Designed using Nektar’s polymer conjugation technology to extend circulating half-life, NKTR-255 can be dosed every 14 or 21 days.

On December 9, 2019 Seven and Eight BioPharmaceuticals Inc. reported that it has signed a clinical research collaboration agreement with Merck (known as MSD outside the US and Canada), through a subsidiary, to explore the combination of Seven and Eight’s BDB001, an immune modulator targeting toll-like receptors (TLR) 7 and 8, and Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in treating patients with advanced solid tumors (Press release, Seven and Eight Biopharmaceuticals, DEC 9, 2019, View Source [SID1234552201]).

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"Seven and Eight is developing a clinical pipeline that aims to address unmet medical needs. This clinical collaboration with Merck represents yet another step in our efforts to help cancer patients who fail to derive desirable clinical benefits from existing therapies."

"We are pleased to enter into a clinical collaboration with Merck," says Dr. Walter Lau, CEO of Seven and Eight. "There has been increasing evidence to show toll-like receptor agonists as a class of immune modulators to stimulate innate immune responses and enhance adaptive anti-tumor immunity. We hope through our joint efforts with Merck, we can explore how to use our lead compound BDB001 together with KEYTRUDA, especially in treating those patients with advanced and difficult-to-treat tumor types."

Dr. Lau adds, "Seven and Eight is developing a clinical pipeline that aims to address unmet medical needs. This clinical collaboration with Merck represents yet another step in our efforts to help cancer patients who fail to derive desirable clinical benefits from existing therapies."

Under the terms of the agreement, Seven and Eight will sponsor and be responsible for the conduct of the clinical study.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

On December 9, 2019 STORM Therapeutics, the biotechnology company focused on the discovery of small molecule therapies modulating RNA epigenetics reported, that its collaborator Dr. Konstantinos Tzelepis, Sir Henry Wellcome Fellow and Visiting Scientist at the Wellcome Sanger Institute, received the ASH (Free ASH Whitepaper)-BSH Abstract Achievement Award for his work on STORM Therapeutics’ lead programme, METTL3, at the 61st Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) held on 7th-10th December 2019 in Orlando, Florida (Press release, STORM Therapeutics, DEC 9, 2019, View Source [SID1234561038]).

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Dr. Tzelepis received the meritorious award for his abstract entitled ‘Pharmacological Inhibition of the RNA m6a Writer METTL3 As a Novel Therapeutics Strategy for Acute Myeloid Leukemia’ at the Abstract Achievement Award Ceremony which was held on Saturday, 7th December 2019 at 3:30pm (EST) at the Orange County Convention Center in Exhibit Hall B2-B4.

Dr. Tzelepis’s work, which was carried out in collaboration with the Wellcome Sanger Institute and the University of Cambridge, was presented in an oral presentation during the "802. Chemical Biology and Experimental Therapeutics: Novel Compounds and Mechanisms of Action" session on Sunday, 8th December 2019 at 9:30am-11:30am (EST) at the Orange County Convention Centre. The abstract and talk encapsulated the ground-breaking work made on targeting RNA modifying enzymes for cancer treatment and described the recent progress made with the METTL3 inhibitor.

STORM has identified small molecule inhibitors of METTL3 that are orally bioavailable and show pronounced anti-tumour efficacy in physiologically relevant, proof of concept animal models of Acute Myeloid Leukaemia (AML). The talk demonstrated that small molecule inhibition of METTL3 produces the same phenotype and effects previously described in one of STORM’s founder scientists’ publications using genetic models and validates METTL3 as a druggable target for cancer.

Keith Blundy, CEO of STORM Therapeutics, said: "STORM is progressing fast in its preclinical work with our multiple programmes to showcase the capabilities of our novel platform. STORM is a pioneer in RNA epigenetics and we are very pleased to hear that our collaborator is being recognized for the partnership research of METTL3. As the first company in the world to demonstrate in vivo activity of an RNA methyltransferase inhibitor, we are excited to be leading the field as we look to develop these highly innovative new treatment options for cancer patients."

On December 9, 2019 Sanofi and Synthorx, Inc. (NASDAQ: THOR), a clinical-stage biotechnology company focused on prolonging and improving the lives of people suffering from cancer and autoimmune disorders, entered into a definitive agreement under which Sanofi will acquire all of the outstanding shares of Synthorx for $68 per share in cash, which represents an aggregate equity value of approximately $2.5 billion (on a fully diluted basis) (Press release, Sanofi, DEC 9, 2019, View Source [SID1234552083]). The transaction was unanimously approved by both the Sanofi and Synthorx Boards of Directors.

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"This acquisition fits perfectly with our strategy to build a portfolio of high-quality assets and to lead with innovation, as you will hear at our Capital Markets Day tomorrow, December 10. Additionally, it is aligned with our goal to build our oncology franchise with potentially practice-changing medicines and novel combinations," says Paul Hudson, Chief Executive Officer, Sanofi.

"Synthorx’s exceptionally novel discovery platform has already produced a molecule that has the potential to become a foundation of the next generation of immuno-oncology combination therapies. By selectively expanding the numbers of effector T-cells and natural killer cells in the body, THOR-707 can be combined with our current oncology medicines and our emerging pipeline of immuno-modulatory agents for treating cancer. Moreover, Synthorx’s pipeline of engineered lymphokines has great promise not only for oncology but also for addressing many autoimmune and inflammatory diseases. " says John Reed, M.D., Ph.D., Global Head of Research & Development at Sanofi.

"We are grateful that Sanofi has acknowledged the value of our Expanded Genetic Alphabet platform and the potential of our pipeline of optimized therapeutics for cancer and autoimmune disorders," says Laura Shawver, Ph.D., President and Chief Executive Officer, Synthorx. "Importantly, Sanofi has a portfolio of therapeutics that holds incredible promise for combining with our cytokine Synthorins to benefit patients around the world. I want to thank our employees and the Sanofi organization for their relentless efforts on behalf of patients."

Enhancing Sanofi’s Immuno-Oncology Franchise

Synthorx’s lead immuno-oncology product candidate, THOR-707, a variant of interleukin-2 (IL-2), is in clinical development in multiple solid tumor types as a single agent and in combination with immune checkpoint inhibitors. It has the potential to become the best-in-class IL-2 therapeutic for the treatment of solid tumors and demonstrate improved pharmacology, less frequent dosing, and therapeutic superiority when compared to other IL-2 compounds.

The addition of THOR-707 and Synthorx’s other earlier-stage cytokine programs to Sanofi’s pipeline will enhance Sanofi’s position in oncology, and in immuno-oncology. We expect IL-2 to become a foundation of future IO-IO combinations as well as offering multiple combination opportunities with Sanofi’s clinical and pre-clinical oncology assets, including with PD-1, CD-38, and molecules that modulate effector T-cells and natural killer cells.

Synergistic with Sanofi’s existing platforms

Synthorx’s Expanded Genetic Alphabet platform is expected to be a source for developing a differentiated therapeutic pipeline. Alone and in combination with other existing Sanofi platforms, including the Nanobody technology, it will enable the company to develop a wide range of novel biologics, including drug conjugates, protein fusions, and multi-specific biologics, with applications beyond oncology and extending to other therapeutic areas.

Transaction Terms

Under the terms of the merger agreement, Sanofi will commence a cash tender offer to acquire all of the outstanding shares of Synthorx common stock for $68 per share in cash for a total enterprise value of approximately $2.35 billion. The $68 per share acquisition price represents a 172% premium to Synthorx’s closing price on December 6, 2019.

The consummation of the tender offer is subject to customary closing conditions, including the tender of at least a majority of the outstanding shares of Synthorx common stock, the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, and other customary conditions. Following the successful completion of the tender offer, a wholly owned subsidiary of Sanofi will merge with Synthorx and the outstanding Synthorx shares not tendered in the tender offer will be converted into the right to receive the same $68 per share in cash paid in the tender offer. The tender offer is expected to commence in December 2019. Sanofi plans to finance the transaction with cash on hand. Subject to the satisfaction or waiver of customary closing conditions, Sanofi expects to complete the acquisition in the first quarter of 2020.

Morgan Stanley & Co. is acting as financial advisor to Sanofi and Weil, Gotshal & Manges LLP is acting as its legal counsel. Centerview Partners LLC is acting as exclusive financial advisor to Synthorx and Cooley LLP is acting as its legal counsel.