On March 26, 2020 Innovent Biologics, Inc. ("Innovent" or the "Company") (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, and Alector, Inc. ("Alector", Nasdaq ticker symbol: ALEC), a clinical stage biotechnology company and leader in the discovery and development of immune system focused therapeutics, jointly reported that they have entered into a licensing agreement to develop and commercialize an anti-SIRP-alpha antibody (Alector’s project code: AL008) for the treatment of oncology indications in China (Press release, Innovent Biologics, MAR 26, 2020, View Source [SID1234555834]).

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AL008 is Alector’s novel antibody targeting the CD47-SIRP-alpha pathway, a potent survival pathway co-opted by tumors to evade the innate immune system. AL008 is a first-in-class SIRP-alpha inhibitor with a unique dual mechanism of action that non-competitively antagonizes the CD47-SIRP-alpha pathway by inducing the internalization and degradation of the inhibitory receptor on macrophages to relieve immune suppression (a "don’t eat me signal") while also engaging Fc gamma to promote immuno-stimulatory pathways that drive anti-tumor immunity.

"Alector has been a pioneer in discovering and developing first-in-class therapeutics modulating the innate immune system since their founding and AL008 represents another successful program from their pipeline," said Dr. Michael Yu, Founder, Chairman and CEO of Innovent Biologics. "Currently, we have a successfully commercialized PD-1 inhibiting antibody, Tyvyt (sintilimab injection), targeting the adaptive immune system and we believe in the importance of modulating innate immune system in oncology as well, especially the SIRP-alpha-CD47 pathway. We believe that AL008 will complement perfectly with our current pipeline, further solidifying our position in this promising space while providing more options to patients in need."

"We are excited to enter into a collaboration with Innovent, one of the premier Chinese biologics companies, which has a fully-integrated multi-functional platform. We have been impressed with the diligence and speed that the Innovent team brings to bear to advance their development programs through clinical trials and beyond. We believe AL008 has great potential and look forward to demonstrating this in the clinic," said Dr. Arnon Rosenthal, Co-Founder and CEO of Alector. "We will be collaborating closely with Innovent to rapidly advance AL008 through clinical trials in order to get this program to benefit more patients both in China and globally."

Under the agreement, Innovent will lead the development and commercialization of the molecule in China, including the manufacturing of the product. Alector will lead development of AL008 outside of China. Financial terms are not disclosed.

About AL008

AL008 is an anti-SIRP-alpha antibody that non-competitively antagonizes the CD47-SIRP-alpha pathway by inducing the internalization and degradation of the inhibitory receptor on macrophages to relieve immune suppression (a "don’t eat me signal) while also engaging Fc gamma to promote immuno-stimulatory pathways that drive anti-tumor immunity. Tumor associated macrophages are associated with poor prognosis in many cancer types and are believed to inhibit the anti-tumor immune response. Targeting the CD47-SIRP-alpha pathway has shown activity in myeloid and lymphoid cancers, but additional agents targeting this pathway are needed to enhance activity and improve safety in solid tumors. AL008 monotherapy reduces tumor growth and enhances M1 macrophage activation in a humanized pre-clinical model. In comparison with other SIRP-alpha targeting antibodies, AL008 binds to all common alleles of SIRP-alpha and has best-in-class potency in tumor cell phagocytosis. AL008 promotes T cell function and in preclinical studies is not associated with depletion of red blood cells or platelets. These data highlight the potential potency of this differentiated mechanism of simultaneously providing immune-activating signals while removing immune-checkpoint signals and demonstrate the potential activity for AL008.

On March 25, 2020 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; Representative Director, President and CEO: Hiroshi Nomura hereinafter called "Sumitomo Dainippon Pharma") reported that, on March 25, 2020, it obtained approval for a partial change in the marketing approval previously acquired in Japan for RETHIO 100 mg for I.V. infusion (generic name: thiotepa; hereinafter, "RETHIO") (Press release, Sumitomo Dainippon Pharma, 25 25, 2020, View Source [SID1234605562]). The change approved at this time involves an additional indication of RETHIO for conditioning treatment prior to autologous hematopoietic stem cell transplantation (auto-HSCT) for malignant lymphoma.

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RETHIO is a drug that Sumitomo Dainippon Pharma launched on May 28, 2019, for an indication of conditioning treatment prior to auto-HSCT for pediatric malignant solid tumors. Malignant lymphoma, which is related to this additional indication, is a type of hemocytes-derived cancer in which lymphocytes, a subpopulation of leukocytes (white blood cells) become cancerous, and typically occurs in lymphoid tissues, such as lymph nodes, spleens, and tonsils, but it often develops in other sites as well. It has been reported that 34,240 persons affected with this disease in FY2016*, making it the most common hematological malignancy in Japanese adults. As with conditioning treatment prior to auto-HSCT for pediatric malignant solid tumors, for which approval was received in 2019, the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs of the Ministry of Health, Labour and Welfare (MHLW) determined similarly high medical need for thiotepa in conditioning treatment prior to auto-HSCT for malignant lymphoma. Accordingly, Sumitomo Dainippon Pharma conducted Phase 1 trials in Japan and subsequently applied for approval of the additional indication.

Sumitomo Dainippon Pharma believes that this approval will allow it to offer a new treatment option for malignant lymphoma patients who need conditioning treatment prior to auto-HSCT, a therapeutic area with a high unmet medical need, thus contributing to improved healthcare.

＊Cancer Incidence of Japan 2016, Cancer and Disease Control Division, Health Service Bureau, MHLW

About autologous hematopoietic stem cell transplantation (auto-HSCT)
Autologous hematopoietic stem cell transplantation is a therapy that aims to reconstruct hematopoietic capacity via intravenous transfusion of normal hematopoietic stem cells of the patient himself/herself after eradicating intractable cancers by conditioning myeloablative treatment prior to transplantation using maximum levels of anti-cancer drugs or radiation.

About the Evaluation Committee on Unapproved or Off-labeled Drugs with High Medical Needs
The Evaluation Committee on Unapproved or Off-label Drugs with High Medical Needs is a committee established to promote the development of unapproved or off-label drugs by pharmaceutical companies that are approved for use in Europe and the United States, etc., but not approved in Japan. It is organized under the MHLW of Japan and consists of academic experts in medical and pharmaceutical fields.

On March 25, 2020 Ono Pharmaceutical Co., Ltd. reported that ONO received a manufacturing and marketing approval of Velexbru (generic name: tirabrutinib hydrochloride) Tablet 80mg ("Velexbru"), a Bruton’s tyrosine kinase ("BTK") inhibitor, for the treatment of recurrent or refractory primary central nervous system lymphoma in Japan (Press release, Ono, MAR 25, 2020, View Source [SID1234584586]).

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This approval is based on the results from a multi-center, open-label, uncontrolled Phase I/II study (ONO-4059-02), evaluating an efficacy and safety of Velexbru in 44 patients with recurrent or refractory primary central nervous system lymphoma (PCNSL), receiving Velexbru orally once daily. In this study, the overall response rate (ORR) assessed by an independent review committee (IRC), a primary endpoint, was 52.9% (9/17 patients) in 17 patients who received 480 mg of Velexbru in the fasting which is the approved dosage and administration this time. Grade 3-4 neutropenia, leucopenia and hypertriglyceridemia each occurred in 11.8% (2/17) of patients. This approval represents that Velexbru is the first BTK inhibitor approved for the treatment of recurrent or refractory PCNSL in the world where no standard of care has been established. On November 27, 2019, ONO also submitted an application of Velexbru in Japan for the treatment of Waldenstrom macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL).

About Primary Central Nervous System Lymphoma (PCNSL)

PCNSL is a malignant lymphoma in which the lesion is localized in the cerebrospinal cord (including the eyes) at the first onset. It is estimated that there are approximately 980 new cases with PCNSL *1, 2 per year in Japan . The signs and symptoms presented by patients with PCNSL vary depending on the site of the lesion, and include localized neuropathy, neuropsychiatric symptoms, symptoms associated with increased intracranial pressure, seizure, eye symptoms, headache, difficulty in movement, cranial neuropathy and radiculopathy. Currently, untreated PCNSL patients receive high-dose methotrexate-based treatment followed by whole-brain radiation therapy, by which a certain patient population shows long-term remissions, but many patients will relapse. There are also refractory patients who do not respond to the drug treatment. Standard treatment has not been established for patients with recurrent or refractory PCNSL, and treatment options are limited for them. Therefore, a new treatment drug is expected for *3 patients with recurrent or refractory PCNSL . *1 : Neurol Med Chir (Tokyo). 2017;57(Supplement 1):9-102. *2 : Jpn J Neurosurg VOL.24 NO.10 2015.10 *3 : Practical Guidelines for Neuro-Oncology 2019

About ONO-4059-02 Study

This study is a multi-center, open-label, single-arm Phase I/II study, evaluating the efficacy and safety of tirabrutinib hydrochloride monotherapy in patients with recurrent or refractory PCNSL. In this study, 44 patients were recruited and received tirabrutinib hydrochloride 320 mg (20 patients), 480 mg (7 patients) and 480 mg fasted (17 patients), once daily in either groups. Patients were treated until disease progression or unacceptable toxicity was observed.

About Velexbru

Velexbru (tirabrutinib hydrochloride), discovered and developed by ONO, is a highly selective, oral BTK inhibitor and has been developed for the treatment of patients with B-cell tumors and autoimmune diseases in Japan. B-cell receptor (BCR) signaling plays a core role in the survival, activation, proliferation, maturation and differentiation of B-cell lymphocyte. The BCR signaling pathway is known to be permanently activated, particularly in B-cell non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia (CLL). Velexbru is expected to have a therapeutic effect because it inhibits BTK, a mediator located downstream of BCR. In December 2014, ONO out-licensed tirabrutinib hydrochloride to Gilead Sciences, Inc. (Gilead) to allow the right to develop and commercialize the product in all countries of the world, except Japan, South Korea, Taiwan, China and ASEAN countries where ONO retains the development and commercialization rights of the product.

Overview of Velexbru Tablet 80mg Product Name Velexbru Tablet 80mg Generic name (JAN) tirabrutinib hydrochloride Indication Relapsed or refractory primary central nervous system lymphoma Dosage and Usually, for adults, administer at 480 mg of tirabrutinib orally once a day administration in the fasting. The dose should be decreased based on patients’ condition. Manufacturer/distributor Ono Pharmaceutical Co., Ltd. Approval date March 25, 2020.

On March 25, 2020 Oasmia Pharmaceutical AB and US based Elevar Therapeutics Inc. reported that they have signed a global strategic partnership deal regarding the commercialization of Oasmia’s anticancer product Apealea (Press release, Oasmia, MAR 25, 2020, View Source [SID1234556577]). The agreement includes milestone payments with a potential of up to USD 678 million depending on Elevar’s achievement of future sales milestones, clinical development milestones and regulatory approval milestones. Elevar will also pay Oasmia double-digit royalties on sales of Apealea. Oasmia will also receive USD 20 million as an upfront payment.

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The worldwide partnership between Oasmia and Elevar grants Elevar the exclusive right to commercialize Apealea, a proprietary formulation of paclitaxel, in all global territories, with the exception of countries in which Oasmia and its partners are already present including Nordics, Baltics, Russia and some other CIS countries[1] in which Oasmia and its partners will continue to drive the commercialization of the product. The arrangement gives Elevar the right to sub-license Apealea to other strategic partners, including, for example, in Europe.

Elevar will be responsible for all regulatory application processes in its territory, including the submission of the approval application to the FDA in the US.

The collaboration between the two companies will include a joint steering committee and working teams in order to optimize the global development, launch and commercialization processes. The partnership will build upon Oasmia’s product development strategy for Apealea, and exploring possible new indications.

Oasmia will remain in sole control over, and will continue to develop, its proprietary technology platform XR17, for use with active pharmaceutical ingredients other than paclitaxel.

"This first major commercial partnership for Oasmia demonstrates both its clinical & regulatory capabilities in getting Apealea approved for the EU and its commercial capabilities by successfully negotiating a global partnership agreement with a US-based company for global exploitation of that product. This is a great achievement. Clinical studies have demonstrated that Apealea is an effective cancer treatment with strong benefits for cancer patients. We will capitalize on this partnership to move Oasmia to its next level of growth by continuing to develop the other compounds in our pipeline. We will also be looking to add new complementary assets. I believe by implementing this partnership, Oasmia has achieved a significant milestone and is on track to become a major oncology player, says Francois R Martelet, CEO at Oasmia.

"At Elevar, we are thrilled to take this exciting anti-cancer drug to the market. We see great potential to commercialize Apealea on a global scale and to develop it further, creating new tools for patients and health care professionals to fight cancer", says Alex Kim, CEO of Elevar.

"This is a great step forward for Oasmia on our way to truly capitalize on the proprietary XR17 technology that has been developed by our company. This deal, together with a lot of hard work the last year, has created a very good platform for the future growth of Oasmia. We have a lot more to achieve", says Jörgen Olsson, Chairman of the Board in Oasmia.

About Apealea
Apealea is a patented, water-soluble, intravenously injectable formulation of paclitaxel, developed using Oasmia’s proprietary technology platform – XR17 – which facilitates the solubility of paclitaxel. Paclitaxel is a chemotherapy medication used to treat a number of types of cancers. Apealea has been authorized for marketing by the European Commission. Apealea in combination with Carboplatin is approved for the treatment of adult patients with first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer.

On March 25, 2020 Amplia Therapeutics Limited (ASX: ATX) ("Amplia" or the "Company") reported that the United States Food and Drug Administration (FDA) has awarded Amplia’s Focal Adhesion Kinase inhibitor (FAKi) AMP945 Orphan-Drug Designation for the treatment of pancreatic cancer (Press release, Amplia Therapeutics, MAR 25, 2020, View Source [SID1234555975]).

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The designation means that Amplia will qualify for waived FDA fees, clinical trial protocol assistance and other incentives. Furthermore, if FDA ultimately approve AMP945 for the treatment of pancreatic cancer, Amplia would qualify for seven years’ market exclusivity in FDA-administered markets.

Amplia is aiming to start a Phase 1 clinical trial of AMP945 in healthy volunteers later this year to confirm that, like other FAKi, it is well tolerated. If this trial is successful, Amplia plans to initiate its first Phase 2 clinical study of AMP945 in cancer patients in 2021. AMP945 has multiple modes of action that make it an appealing candidate for incorporation into treatment regimes for hard-to-treat solid cancers such as pancreatic, ovarian, breast and lung.

Commenting on the Orphan Drug Designation, Professor Paul Timpson, a member of Amplia’s Scientific Advisory Board noted that "Pancreatic cancer is a seriously unmet medical need and FDA’s designation of AMP945 as an orphan-drug underlines global regulatory agencies’ interest in supporting novel treatments for this deadly disease".

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics