On July 14, 2020 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that the Company entered into an exclusive license agreement with Baylor College of Medicine covering alloimmune defense receptors, a first-in-class approach that renders off-the-shelf allogeneic cell products resistant to host immune rejection (Press release, Fate Therapeutics, JUL 14, 2020, View Source [SID1234561848]). Preclinical studies published in the journal Nature Biotechnology (View Source) demonstrate that allogeneic cells engineered with a novel alloimmune defense receptor (ADR) are protected from both T- and NK-cell mediated rejection, and provide proof-of-concept that ADR-expressing allogeneic cell therapies can durably persist in immunocompetent recipients.

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"Allogeneic cell therapy requires a patient to endure systemic lympho-conditioning to suppress the immune system and mitigate cellular rejection, often resulting in severe blood cell deficiencies and related toxicities. There is great interest in strategies that enable allogeneic cells to overcome host immunity and evade immune rejection while maintaining a patient’s functional hematopoietic system," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "The published preclinical data provide compelling evidence that allogeneic cell therapies armed with novel alloimmune defense receptors can effectively abrogate both T- and NK-cell rejection responses and can persist and remain functional in immunocompetent patients."

ADRs are synthetic receptors that selectively recognize cell surface receptors, such as 4-1BB, that are uniquely expressed on activated lymphocytes, which are responsible for host immune rejection. The published preclinical findings show that the arming of allogeneic T cells with an ADR selectively eliminates alloreactive T and NK cells, while sparing resting lymphocytes. Importantly, in in vivo preclinical models of cancer, allogeneic T cells expressing both an ADR and a CD19-targeted chimeric antigen receptor (CAR) demonstrated increased expansion and persistence, resulting in sustained tumor eradication and a long-term survival benefit compared to conventional CD19-targeted CAR T cells.

"There is tremendous promise for the use of off-the-shelf allogeneic cells as replacement therapy. One of the most significant barriers to overcome is host immunity, which can prevent the engraftment of allogeneic cells and the long-term replacement of a patient’s damaged or dysfunctional cells," said Maksim Mamonkin, Ph.D., Assistant Professor, Center for Cell and Gene Therapy, Baylor College of Medicine and the senior author on the Nature Biotechnology publication. "We are excited for Fate Therapeutics to explore the use of alloimmune defense receptors in the development of rejection-resistant, iPSC-derived cellular therapies."

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

On July 14, 2020 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) reported that the Australian Therapeutic Goods Administration (TGA) has approved QINLOCK (ripretinib), a switch-control tyrosine kinase inhibitor, for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib (Press release, Deciphera Pharmaceuticals, JUL 14, 2020, View Source [SID1234561847]). The QINLOCK Marketing Authorisation Application was approved by the TGA under Project Orbis, an initiative of the U.S. Food and Drug Administration’s (FDA) Oncology Center of Excellence designed to provide a framework for concurrent submission and review of oncology products among international partners. QINLOCK is also approved by the U.S. FDA for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib, and authorized by Health Canada for the treatment of adult patients with advanced GIST who have received prior treatment with imatinib, sunitinib, and regorafenib.

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"We would like to thank the team at the Therapeutic Goods Administration for their collaboration in the review and approval of QINLOCK in Australia," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "We believe that QINLOCK has the potential to transform the GIST treatment landscape and are committed to ensuring its global commercial availability."

The TGA’s approval was based on efficacy results from the pivotal global Phase 3 INVICTUS study of QINLOCK in patients with advanced GIST as well as combined safety results from INVICTUS and the Phase 1 study of QINLOCK. In INVICTUS, QINLOCK demonstrated a median progression-free survival of 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001). In addition, QINLOCK demonstrated a median overall survival of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).

The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (PPES), and vomiting. Adverse reactions resulting in permanent discontinuation occurred in 8% of patients, dosage interruptions due to an adverse reaction occurred in 24% of patients and dose reductions due to an adverse reaction occurred in 7% of patients who received QINLOCK.

About QINLOCK (ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. QINLOCK inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved in GIST, as well as the primary exon 17 D816V mutation involved in systemic mastocytosis, or SM. QINLOCK also inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

QINLOCK is approved by the U.S. FDA for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. It is also approved by Health Canada for the treatment of adult patients with advanced GIST who have received prior treatment with imatinib, sunitinib, and regorafenib and by the Australian Therapeutic Goods Administration for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

Deciphera Pharmaceuticals is developing QINLOCK for the treatment of KIT and/or PDGFRα-driven cancers, including GIST, SM, and other cancers. Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of QINLOCK in Greater China (Mainland China, Hong Kong, Macau, and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for QINLOCK in the rest of the world.

About GIST

Gastrointestinal stromal tumor (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in European and other countries. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 80% of cases, or in PDGFRα kinase, representing approximately 6% of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.

On July 14, 2020, Cytokinetics, Incorporated ("Cytokinetics") reported that it entered into a License and Collaboration Agreement (the "License Agreement") with Ji Xing Pharmaceuticals Limited ("Ji Xing"), an entity sponsored by investment funds managed or advised by RTW Investments, LP, pursuant to which Cytokinetics granted to Ji Xing an exclusive license to develop and commercialize Cytokinetics’ proprietary small molecule cardiac myosin inhibitor product referred to as CK-274 (the "Product") in the greater China region, including mainland China, Hong Kong, Macau, and Taiwan (Filing, 8-K, Cytokinetics, JUL 14, 2020, View Source [SID1234561846]).

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Under the terms of the License Agreement, Cytokinetics will receive from Ji Xing an upfront payment of $25 million. Cytokinetics may be eligible to receive from Ji Xing milestone payments totaling up to $200 million for the achievement of certain development and commercial milestone events in connection to the Product in the field of obstructive hypertrophic cardiomyopathy ("oHCM") and/or non-obstructive hypertrophic cardiomyopathy ("nHCM") and other indications. In addition, Ji Xing will pay to Cytokinetics tiered royalties in the low-to-high teens range on the net sales of the Product in the greater China region, subject to certain reductions for generic competition, patent expiration and payments for licenses to third party patents.

Ji Xing will be responsible for the development and commercialization of the Product at its own cost and is required to use diligent efforts to develop and commercialize the Product in the greater China region. The development of the Product will be initially focused on hypertrophic cardiomyopathy, and Ji Xing will have the opportunity to participate in Cytokinetics’ global pivotal clinical trials of the Product. Cytokinetics will supply the Product to Ji Xing either as a finished product or as an active pharmaceutical ingredient.

The License Agreement, unless terminated earlier, will continue on a market-by-market basis until expiration of the relevant royalty term. Ji Xing has the right to terminate the License Agreement for convenience. Each party may terminate the License Agreement for the other party’s uncured material breach, insolvency, or failure to perform due to extended force majeure events. Cytokinetics may also terminate the License Agreement if Ji Xing challenges Cytokinetics’ patents or undergoes certain change of control transactions. Product rights will revert to Cytokinetics upon termination, and, under certain circumstances, subject to a low single digit royalty payment on the net sales of the Product in the greater China region.

The foregoing description of the material terms of the License Agreement does not purport to be complete and is qualified in its entirety by reference to the complete text of the License Agreement, a copy of which Cytokinetics intends to file, with confidential terms redacted, with the United States Securities and Exchange Commission (the "SEC") as an exhibit to Cytokinetics’ Quarterly Report on Form 10-Q for the quarterly period ending September 30, 2020.

Funding Agreement

On July 14, 2020, Cytokinetics entered into a Funding Agreement (the "Funding Agreement") with Dolya Holdco 19 Designated Activity Company ("RTW"), an affiliate of RTW Investments, LP. Pursuant to the Funding Agreement, RTW has committed to provide up to $90 million ("Funding Commitment") to fund Cytokinetics’ development and commercialization of the Product in nHCM and oHCM. $45 million of the Funding Commitment will be available, at Cytokinetics’ option, if certain clinical trial milestones of the Product for oHCM are achieved by January 14, 2023, and $45 million of the Funding Commitment will be available, at Cytokinetics’ option, if certain clinical trial milestones of the Product for nHCM are achieved by January 14, 2024. If Cytokinetics develops the Product in another indication, RTW and Cytokinetics will negotiate an additional funding commitment from RTW to fund Cytokinetics’ development and commercialization of the Product in such other indication (other than oHCM or nHCM).

In exchange for the Funding Commitment and upon receipt of such funding from RTW, Cytokinetics has agreed to make payments to RTW ("Product Royalty Payment") equal to 2%, if RTW funds $45 million of the Funding Commitment, or 4%, if RTW funds the full $90 million of the Funding Commitment, in each case in respect of net sales of the Product by Cytokinetics and any of its licensees in the United States, the European Union, Switzerland, the United Kingdom and certain other countries in Europe (the "Territory"). The Product Royalty Payment with respect to the Product in a country in the Territory will be terminated upon the later of (i) the last patent expiration of patents related to the Product in such country and (ii) the expiration of regulatory exclusivities for the Product in such country.

The Funding Agreement contains customary representations and warranties of Cytokinetics and RTW, including with respect to organization, authorization and tax matters, and certain covenants with respect to payment, reports, intellectual property, out-licenses, and certain other actions with respect to the Product. After Cytokinetics receives funding from RTW

and until such time that RTW receives Product Royalty Payments above a certain agreed threshold, (i) RTW will be granted a security interest in the intellectual property located in the United States and accounts receivable related to the Product and (ii) Cytokinetics will be subject to a negative pledge in respect of certain assets related to the Product.

The Funding Agreement contains customary conditions to disbursement, which may include the consent of Cytokinetics’ senior secured lenders at the time of disbursement.

The foregoing description of the material terms of the Funding Agreement does not purport to be complete and is qualified in its entirety by reference to the complete text of the Funding Agreement, a copy of which Cytokinetics intends to file, with confidential terms redacted, with the SEC as an exhibit to Cytokinetics’ Quarterly Report on Form 10-Q for the quarterly period ending September 30, 2020.

Royalty Purchase Agreement.

On July 14, 2020, Cytokinetics entered into a Royalty Purchase Agreement (the "Royalty Purchase Agreement") with RTW, pursuant to which Cytokinetics will sell its right to receive certain payments on the net sales of products containing the compound mavacamten, a cardiac myosin inhibitor ("Mavacamten Royalty") under the Research Collaboration Agreement, dated August 24, 2012, between Cytokinetics and MyoKardia, Inc. (as amended, the "Collaboration Agreement") to RTW for an one-time payment of $85 million. Such purchase price will be paid to Cytokinetics at a closing, which is expected to occur on or before October 12, 2020 or such later date as may be agreed by the parties. The closing of the transactions contemplated by the Royalty Purchase Agreement are subject to customary closing conditions, as well as the parties obtaining the consent of MyoKardia to the sale of the Mavacamten Royalty to RTW, as well as obtaining the consent of its senior secured lenders, Oxford Finance LLC and Silicon Valley Bank.

The Royalty Purchase Agreement contains customary representations and warranties of Cytokinetics and RTW, including with respect to organization, authorization and tax matters, and certain covenants with respect to royalty payments, and certain other actions with respect to the Collaboration Agreement.

The foregoing description of the material terms of the Royalty Purchase Agreement does not purport to be complete and is qualified in its entirety by reference to the complete text of the Royalty Purchase Agreement, a copy of which Cytokinetics intends to file, with confidential terms redacted, with the SEC as an exhibit to Cytokinetics’ Quarterly Report on Form 10-Q for the quarterly period ending September 30, 2020.

Common Stock Purchase Agreements

On July 14, 2020, Cytokinetics entered into Common Stock Purchase Agreements (each, a "CSPA") with each of RTW Master Fund, Ltd., RTW Innovation Master Fund, Ltd. and RTW Venture Fund Limited (collectively, the "RTW Investors").

The CSPAs provide for the sale and issuance of an aggregate of 2,000,000 shares of common stock of Cytokinetics (the "Shares") at a price per share of $25.00 and an aggregate purchase price of $50 million, and the closing is to occur on July 14, 2020. The RTW Investors have agreed to certain trading and other restrictions with respect to the Shares, including a restriction on sales or other transfers of the Shares, subject to certain exceptions, for a period of two years from the closing date, which period will be extended if Cytokinetics initiates a pivotal clinical trial of CK-274 in oHCM or nHCM prior to the end of such two year period.

The foregoing description of the material terms of the CSPAs does not purport to be complete and is qualified in its entirety by reference to the complete text of the form of CSPA, a copy of which Cytokinetics intends to file, with confidential terms redacted, with the SEC as an exhibit to Cytokinetics’ Quarterly Report on Form 10-Q for the quarterly period ending September 30, 2020.

On July 14, 2020 Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a biotechnology company devoted to development of next-generation medicines to improve the lives of patients with immune-mediated diseases, reported block sales of an aggregate of 4,580,361 shares of common stock to Perceptive Advisors, LLC and Avidity Partners Management LP, two leading healthcare-focused investment funds, under Aldeyra’s previously announced at-the-market offering program (Press release, Aldeyra Therapeutics, JUL 14, 2020, View Source [SID1234561844]). The shares were sold for a price of $4.25 per share. Aggregate gross proceeds, before deducting commissions, were approximately $19.5 million. The sales completed Aldeyra’s previously disclosed at-the-market offering program and no further sales will be made under this program. Jefferies, LLC served as sales agent under the at-the-market offering program.

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Aldeyra anticipates using the net proceeds from the sales for the continued development of the company’s lead compound reproxalap and other product candidates, as well as for debt maintenance, working capital, and other general corporate purposes. Based on current operating plans, cash, cash equivalents, and marketable securities are sufficient to fund operations through the end of 2022, including potential NDA approvals for reproxalap, a first-in-class topical ocular reactive aldehyde species (RASP) inhibitor, in dry eye disease and allergic conjunctivitis, assuming positive clinical trial results, and planned NDA submissions, acceptances, and approvals. Use of proceeds are also expected to include the continuation of Part 1 of the Phase 3 GUARD Trial for proliferative vitreoretinopathy, a rare retinal disease with no approved therapy, and Phase 2 clinical testing of ADX-629, an orally administered RASP inhibitor, in inflammatory diseases.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the company’s common stock nor shall there be any sale of such common stock in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On July 14, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that its investigational CD20xCD3 T-cell engaging bispecific mosunetuzumab has been granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma who have received at least two prior systemic therapies (Press release, Hoffmann-La Roche, JUL 14, 2020, View Source [SID1234561840]).

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"We are pleased that the FDA has granted Breakthrough Therapy Designation to mosunetuzumab, recognising the promising early efficacy data for this molecule and the remaining unmet need in follicular lymphoma," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Indeed, we are excited by the potential of both our CD20xCD3 bispecific antibodies – mosunetuzumab and glofitamab – in development for difficult-to-treat lymphomas, and remain committed to developing innovative therapies to improve outcomes for patients."

This designation was granted based on encouraging efficacy results observed in the phase I/Ib GO29781 study [NCT02500407] investigating mosunetuzumab in R/R non-Hodgkin lymphoma (NHL). The safety profile of this T-cell engaging bispecific was consistent with its mechanism of action. Results from this study were previously presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2019 Annual Meeting.

BTD is designed to accelerate the development and review of medicines intended to treat serious or life-threatening conditions with preliminary evidence that indicates they may demonstrate a substantial improvement over existing therapies. This is the 34th BTD for Roche’s portfolio of medicines, and the 10th designation for its haematology portfolio.

A robust clinical development programme for mosunetuzumab is ongoing across a number of lymphoma indications and earlier lines of treatment, investigating the molecule alone and in combination to identify where mosunetuzumab may be able to provide benefit over current treatment options. This includes further investigation of mosunetuzumab in combination with Roche’s Polivy (polatuzumab vedotin) and Tecentriq (atezolizumab) as well as with chemotherapy regimens and non-Roche molecules.

About mosunetuzumab
Mosunetuzumab is an investigational CD20xCD3 T-cell engaging bispecific designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. This dual targeting activates and redirects a patient’s existing T-cells to engage and eliminate target B-cells by releasing cytotoxic proteins into the B-cells. Mosunetuzumab has a structure similar to that of a natural human antibody in that it has two ‘Fab’ regions, but is different from naturally-occurring antibodies in that one ‘Fab’ region targets CD20 and the other ‘Fab’ region targets CD3. A robust clinical development programme for mosunetuzumab is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with CD20-positive B-cell non-Hodgkin lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.

About the GO29781 study
The GO29781 study [NCT02500407] is a phase I/Ib, multicentre, open-label, dose-escalation study evaluating the safety and pharmacokinetics of mosunetuzumab in people with relapsed or refractory B-cell non-Hodgkin lymphoma. Outcome measures include best objective response rate by revised International Working Group criteria, maximum tolerated dose, and tolerability.

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes idasanutlin, a small molecule which inhibits the interaction of MDM2 with p53; T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3; Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.