On October 23, 2018 AstraZeneca, and its global biologics research and development arm MedImmune, reported a new multi-term agreement with Innate Pharma (Innate), building on an existing collaboration, aimed at accelerating each company’s oncology portfolio and bringing new medicines to patients more quickly (Press release, AstraZeneca, OCT 23, 2018, View Source [SID1234530224]). The extended collaboration will enrich AstraZeneca’s immuno-oncology (IO) portfolio with pre-clinical and clinical potential new medicines.

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AstraZeneca will obtain full oncology rights to the first-in-class humanised anti-NKG2A antibody, monalizumab, expanding its partnership with Innate from the initial collaboration announced in 2015. AstraZeneca also gains option rights to IPH5201, an antibody targeting CD39, as well as four preclinical molecules from Innate’s pipeline. Innate is licensing the US and EU commercial rights to recently FDA-approved Lumoxiti (moxetumomab pasudotox) for hairy cell leukaemia (HCL).

Pascal Soriot, Chief Executive Officer, said: "Our expanded collaboration with Innate Pharma enables us to further strengthen our leadership in immuno-oncology, and to explore the potential of next-generation immuno-oncology pathways, together with the world-class scientific team of Innate. Today’s agreement also secures the long-term commercialisation of the recently FDA approved rare disease medicine, Lumoxiti, through dedicated focus and investment by Innate Pharma."

Mondher Mahjoubi, Chief Executive Officer of Innate Pharma, said: "Today is a defining moment for Innate Pharma as we transition to become a fully-integrated oncology-focused biotech. Lumoxiti is a major therapeutic innovation for patients who suffer from relapsed/refractory hairy cell leukaemia, and we are proud to be in a position to address a significant unmet medical need. Our commercial team will be focused on rare cancers and generate more value as our own haemato-oncology proprietary pipeline develops."

Monalizumab

Building on a 2015 collaboration with Innate, AstraZeneca is exercising its option to obtain full oncology rights to monalizumab, a first-in-class humanised anti-NKG2A antibody. NKG2A is a checkpoint receptor expressed on tumour-infiltrating cytotoxic T-cells and natural killer (NK) cells that inhibits their anti-cancer functions. The companies currently share Phase II development for monalizumab in combination trials in both head and neck and colorectal cancer, with additional trials underway in other solid tumours.

Results from a single-arm Phase II trial of monalizumab in combination with cetuximab in head and neck cancer patients were presented at the ESMO (Free ESMO Whitepaper) 2018 Congress (European Society of Medical Oncology), showing deep and durable responses in 40 patients with ORR of 27.5%, progression free survival of 5.0 and overall survival of 10.3 months, respectively. Among the 40 patients enrolled in the cohort expansion, the safety findings were consistent with previously-presented data at AACR (Free AACR Whitepaper) 2017 and 2018 (Abstract #1049PD).

CD39 and additional molecules

AstraZeneca is entering into a development collaboration and option for further co-development and co-commercialisation with Innate for its CD39 monoclonal antibody, IPH5201.

CD39 is a membrane-bound extracellular enzyme overexpressed on both regulatory T-cells and tumour cells in several cancer types. CD39 plays an important role in promoting immunosuppression through the pathway that degrades adenosine triphosphate (ATP) into adenosine. It is increasingly recognised that the adenosine pathway is critical in tumour immunosuppression and will complement AstraZeneca’s current portfolio in this area.

In addition, Innate grants AstraZeneca an option to exclusively license four molecules to be agreed upon from Innate’s preclinical portfolio, increasing the breadth and depth of AstraZeneca’s immuno-oncology portfolio.

Lumoxiti

Innate is licensing the US commercial rights of AstraZeneca’s recently FDA-approved treatment for HCL, Lumoxiti. Innate, with support from AstraZeneca, will continue EU development and commercialisation, pending regulatory submission and approval.

Lumoxiti is a CD22-directed cytotoxin and a first-in-class medicine in the US for adult patients with relapsed or refractory HCL who have received at least two prior systemic therapies, including treatment with a purine nucleoside analogue. Approximately 1,000 people are diagnosed with HCL in the US each year, a subset of which would be eligible for Lumoxiti. Innate will recognise revenues and co-commercialise Lumoxiti with AstraZeneca in the US and will take full responsibility by mid-2020.

Financial considerations

Innate will pay AstraZeneca $50 million upfront for Lumoxiti, and $25 million for future commercial and regulatory milestones, in consideration for its intellectual property and clinical and manufacturing development of the medicine. This income will be recorded as Other Operating Income by AstraZeneca.

AstraZeneca will pay Innate $100 million in the first quarter of 2019 for the expansion of the monalizumab collaboration. Additional financial arrangements related to monalizumab are detailed and available in the 2015 collaboration announcement.

Further, AstraZeneca will pay Innate $50 million upfront for the development collaboration and option for further co-development and co-commercialisation of Innate’s CD39 monoclonal antibody, IPH5201, plus an option exercise fee, milestones and royalties. Innate will have the potential for co-promotion and profit sharing in the EU.

AstraZeneca will also pay Innate $20 million upfront for an exclusive license option on four to-be-agreed molecules from Innate’s preclinical portfolio. These options can be exercised before the molecules reach clinical development, triggering an option exercise fee in addition to milestones and royalties. Innate will have the potential for co-promotion and profit sharing in the EU, dependent on future progress.

Given the long-term collaboration between the two companies, AstraZeneca will acquire a 9.8% equity stake in Innate Pharma through the issuance of 6,260,500 new shares to AstraZeneca at €10/share. Issuance of the new shares is expected to take place on or about 25 October 2018.

On October 23, 2018 IDEAYA Biosciences, Inc., reported it has entered into an exclusive license agreement with Novartis to develop and commercialize Novartis’ LXS196, a Phase 1 protein kinase C (PKC) inhibitor for the treatment of cancers with GNAQ and GNA11 mutations (Press release, Ideaya Biosciences, OCT 23, 2018, View Source [SID1234535455]).

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LXS196, which will be recoded as IDE196 by IDEAYA for future development, is a potent small molecule inhibitor of PKC demonstrating early clinical activity and tolerability in an ongoing Phase 1 study of IDE196 for patients with metastatic uveal melanoma (MUM). IDE196 is active across multiple PKC isoforms and is highly selective relative to other kinases. MUM is an orphan disease of high unmet medical need, with median overall survival of approximately 10 months and no FDA approved therapies.

"There are no approved therapies for metastatic uveal melanoma, and continued development of promising clinical stage agents, such as IDE196, with a clear genetic biomarker rationale to treat patients that harbor GNAQ and GNA11 mutations through PKC are paramount," said Dr. Sophie Piperno‐Neumann, M.D., LXS196 Study Investigator and Medical Oncologist at Institute Curie, Paris, France.

IDEAYA will continue development in metastatic uveal melanoma and will also explore a tumor agnostic basket study of solid tumors with mutations of GNAQ and GNA11. Both GNAQ and GNA11 mutations are listed in multiple diagnostic panels, including the FoundationOne CDx NGS panel, FoundationOne Liquid Biopsy Panel, and the Guardant360 Liquid Biopsy panel, which provides a clear path towards identifying patients. IDEAYA is also evaluating the potential use of IDE196 to target various PKC fusion isoforms.

Novartis is conducting an ongoing Ph1 clinical trial, entitled "A Phase I, multi-center, open-label, study of LXS196, an oral protein kinase C inhibitor, in patients with metastatic uveal melanoma" (ClinicalTrials.gov Identifier: NCT02601378). In the ongoing trial, IDE196 is being studied as a single-agent and in combination therapy with HDM201, Novartis’ human double minute 2 (HDM2) inhibitor, an important negative regulator of the p53 tumor suppressor. Notably, approximately 90% of metastatic uveal melanoma patients harbor activating mutations in GNA11 or GNAQ.

"Targeting PKC, a pathway which is active in this disease, may result in improved clinical outcomes, and the data with IDE196 treatment thus far demonstrate objective responses, with tolerability that will enable ongoing and future monotherapy and combination trials," said Dr. Ellen Kapiteijn, M.D. Ph.D., LXS196 Study Investigator and Medical Oncologist at Leiden University Medical Center, Leiden, Netherlands.

Under the exclusive license, Novartis increased its equity ownership in IDEAYA, and is due future milestones and royalties, and Novartis will continue the ongoing IDE196 monotherapy and combination study with the Novartis HDM201 compound. IDEAYA has exclusive rights for further clinical development of IDE196, together with unrestricted rights to commercialize worldwide.

"IDE196 enhances our robust precision medicine pipeline, and we are ecstatic to develop this first-in-class therapy for cancer patients who harbor activating mutations of GNAQ and GNA11," said Yujiro Hata, Chief Executive Officer of IDEAYA. "Novartis has been an investor in IDEAYA since the Series A, so we are pleased to enter into this agreement and further enhance our strategic relationship."

On October 23, 2018 Humanetics Corporation (Humanetics) reported that it has been invited to present at the annual meeting of the American Society for Radiation Oncology (ASTRO) being held October 21st through the 24th in San Antonio, Texas. Dr. Michael Kurman, M.D., Chief Medical Officer for Humanetics, will be presenting an overview of the study design and providing an update on the status of the Company’s on-going, multi-site, Phase 1b/2a trial in non-small cell lung cancer patients (Press release, Humanetics, OCT 23, 2018, View Source [SID1234530068]). The trial is investigating the safety and efficacy of BIO 300, a new drug candidate focused on mitigating toxicities to normal tissues resulting from cancer radiotherapy.

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Lung cancer is the most common cause of cancer-related deaths in the United States and affects more than 230,000 individuals per year. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, comprising approximately 87% of all cases. A common treatment for NSCLC is radiotherapy, which is often accompanied by chemotherapy. Radiation can cause unwanted side-effects to otherwise healthy tissue surrounding the tumor or in the path of the radiation beam. These effects include esophagitis, pulmonary pneumonitis and fibrosis, all of which can contribute to lasting health problems and in severe cases can be fatal.

"Drugs that can prevent the unwanted side effects of radiotherapy are an urgent need for patients," said Dr. Charles Simone, Associate Professor of Radiation Oncology and Medical Director of the Maryland Proton Therapy Center in Baltimore, Maryland. "Radiotherapy is an important standard of care and its use is forecast to grow. Drugs such as BIO 300 have the potential to significantly improve the quality of life and outcomes for our patients." Dr. Simone is serving as a Principal Investigator for the BIO 300 clinical trial.

BIO 300 is an oral medication, taken once daily by the patient prior to their radiation treatment. Its properties as a radioprotectant were discovered by researchers at the U.S. Department of Defense, where it was studied as a potential agent to be used by warfighters to prevent injury from radiation on the battlefield. Humanetics acquired the rights to the drug and has active development programs ongoing in both oncology and for biodefense.

On October 23, 2018 Cerus Corporation (Nasdaq:CERS) reported that its third quarter results will be released on Thursday, November 1, 2018, after the close of the stock market Cerus Corporation (Nasdaq:CERS) announced today that its third quarter results will be released on Thursday, November 1, 2018, after the close of the stock market. The company will host a conference call and webcast at 4:15 P.M. EDT that afternoon, during which management will discuss the Company’s financial results and provide a general business overview and outlook.

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To access the live webcast, please visit the Investor Relations page of the Cerus website at View Source Alternatively, you may access the live conference call by dialing (866) 235-9006 (U.S.) or (631) 291-4549 (international).

A replay will be available on the company’s website, or by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and entering conference ID number 7095077. The replay will be available approximately three hours after the call through November 15, 2018.. The company will host a conference call and webcast at 4:15 P.M. EDT that afternoon, during which management will discuss the Company’s financial results and provide a general business overview and outlook.

To access the live webcast, please visit the Investor Relations page of the Cerus website at View Source Alternatively, you may access the live conference call by dialing (866) 235-9006 (U.S.) or (631) 291-4549 (international).

A replay will be available on the company’s website, or by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and entering conference ID number 7095077. The replay will be available approximately three hours after the call through November 15, 2018.

On October 23, 2018 Context Therapeutics reported Phase 1 data for its investigational new drug, Apristor (Onapristone extended release), an oral progesterone receptor antagonist that is being developed for progesterone receptor-positive (PR+) cancers (Press release, Context Therapeutics, OCT 23, 2018, View Source [SID1234530069]). Data from the study showed that Apristor, a novel extended release formulation of onapristone, was well tolerated and provided a clinical benefit in patients with previously treated recurrent or metastatic progesterone receptor-driven breast, ovarian and endometrial cancers. These findings were published in the medical journal PLOS One and can be accessed here.

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"I’m encouraged by the early data seen in this Phase 1 study of Apristor. Apristor appears to be well tolerated, with responses seen across a broad range of PR+ cancers," commented Paul Cottu, M.D., Ph.D., Deputy Head, Department of Oncology, Institute Curie, and lead investigator for the trial. "Many hormonally-driven malignancies are difficult to treat, and new agents are clearly needed. Targeted therapies, including Apristor, have the potential not only to add therapeutic options for our patients but also to reduce or delay the need for chemotherapy, possibly changing the way many of these malignancies are treated."

"Context is pleased with the Phase 1 Apristor study results demonstrating clinical efficacy across PR+ cancers in heavily pretreated patients who are typically unresponsive to currently approved hormonal treatments," stated Martin Lehr, CEO of Context Therapeutics. "We believe Apristor has the potential to be the first anti-progestin approved to treat cancer and we are rapidly advancing Apristor into multiple Phase 2 trials with a goal of addressing significant medical needs."

Apristor Phase 1 Data in Patients with PR+ Breast, Ovarian, or Endometrial Cancer

Design
52 patients were randomized to five cohorts of Apristor (onapristone extended release tablets 10, 20, 30, 40 or 50 mg BID; n=46), or immediate release onapristone 100 mg QD (n=6) until progressive disease or intolerability. Primary endpoint was to identify the recommended phase 2 dose. Secondary endpoints included safety, clinical benefit and pharmacokinetics.

Results
Tumor diagnosis includes: endometrial carcinoma 12; breast cancer 20; ovarian cancer 13; and other 7. Median age was 64 (36-84). No dose limiting toxicity was observed with reported liver function test elevation related only to liver metastases. The recommended Phase 2 dose (RP2D) was 50mg BID. For patients on Apristor (n=46), dose responsive activity was noted, and 20% (9 of 46) patients had clinical benefit ≥24 weeks. The most common side effects were asthenia and low-grade, transient gamma-glutamyl transferase elevations.

Clinical Activity
Tumor assessments strongly suggested anti-cancer efficacy, even in heavily pretreated patients. In Apristor treated patients, 20 of 46 patients experienced stable disease as best response and 9 of 46 patients had durable disease stabilization.

The new extended release formulation of Onapristone (Apristor) was well tolerated and resulted in clinical benefit in heavily pretreated patients with ovarian, breast and uterine endometrial cancers. The recommended Phase 2 dose for Apristor is 50mg BID. There were no grade 3-4 LFT elevations in the absence of progressive liver metastases, no new safety signals were observed, and dose limiting toxicity was not observed. The data support the development of Apristor in PR+ cancers.

About Apristor

Apristor, an investigational new drug, is an oral progesterone receptor (PR) antagonist. PR is an oncogene that is enriched in up to 70% of all breast, ovarian, and endometrial cancers. Apristor is being developed to treat metastatic breast, ovarian and endometrial cancers.