On October 2, 2019 Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell therapies, reported that clinical data on the company’s pipeline of candidates will be presented at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held November 6-10, 2019, in Washington, D.C (Press release, Celyad, OCT 2, 2019, View Source [SID1234540004]).

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"SITC 2019 remains an important avenue for us to provide updated results of our clinical programs in metastatic colorectal cancer, and in particular, data from the industry’s first trial investigating an ‘off-the-shelf,’ non-gene edited allogeneic CAR-T candidate for the treatment of solid tumors," commented Dr. Frédéric Lehmann, VP of Clinical Development & Medical Affairs at Celyad. "In addition, disclosing clinical and scientific data from the SHRINK and alloSHRINK dose-escalation Phase 1 trials in parallel will allow the comparison of results obtained with an autologous CAR-T and its equivalent allogeneic version. As such, this comparison highlights our efforts to understand analytical development in CAR-T space and our ongoing mission to get this much-needed therapy to people living with this deadly cancer, for which there are few treatment options".

Poster Details:

Abstract P147: Effect of chemotherapy on cellular kinetics of NKG2D-based CAR T-cells in metastatic colorectal cancer patients.
Date & Time: November 8, 7:00 am. – 8:00 p.m.
Abstract P330: Results from the completed dose-escalation of the alloSHRINK phase I study evaluating the allogeneic NKG2D-based CAR T-cell therapy CYAD-101 in metastatic colorectal cancer patients
Date & Time: November 9, 7:00 am. – 8:30 p.m. EDT
Abstract P331: Results from the completed dose-escalation phase I SHRINK study evaluating the autologous NKG2D-based CAR T-cell therapy CYAD-01 in metastatic colorectal cancer patients
Date & Time: November 8, 7:00 am. – 8:00 p.m. EDT

www.celyad.com | 1

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Press Release

02 October 2019

07:00 am CEDT

Background on SHRINK and alloSHRINK Trials

SHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and activity of CYAD-01 administered concurrently with FOLFOX chemotherapy in patients with metastatic colorectal cancer (mCRC). Patients will receive six cycles of FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) chemotherapy every two weeks and three administrations of CYAD-01 every two weeks.

alloSHRINK is an open-label, dose-escalation Phase 1 trial assessing the safety and clinical activity of CYAD-101 administered concurrently with FOLFOX chemotherapy in patients with refractory mCRC. Similar to the SHRINK trial for CYAD-01, patients will receive six cycles of FOLFOX chemotherapy every two weeks and three administrations of CYAD-101 every two weeks.

On October 2, 2019 AIVITA Biomedical, Inc., a biotech company specializing in innovative stem cell applications, reported the publication of an article titled "Preliminary observations on soluble programmed death-1 protein as a prognostic and predictive biomarker in patients with metastatic melanoma treated with patient-specific autologous vaccines" in the oncology journal Oncotarget (Press release, AIVITA Biomedical, OCT 2, 2019, View Source [SID1234540003]). Robert O. Dillman, M.D., Chief Medical Officer at AIVITA, and other key members of the AIVITA team authored the article.

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The publication suggests that because of its role as an immune checkpoint, levels of soluble programmed cell death protein-1 (sPD-1) could be useful as a prognostic biomarker or predictive biomarker in cancer patients treated with vaccines. The authors theorized that very low blood levels of sPD-1 may indicate lack of an existing anti-cancer immune response, while very high levels may indicate an active immune response that is suppressed. In between these extremes, a decrease in PD-1 following cancer vaccine injections may indicate an enhanced immune response that has not been suppressed.

Blood samples were obtained at baseline and four weeks later during a randomized trial in which patients with metastatic melanoma were treated with either AIVITA’s immunotherapy, or an active control article. Median survival was more than twice as long in patients treated with AIVITA’s immunotherapy. The combination of a very low baseline sPD-1, or absence of a very high PD-1, at baseline followed by a decline in sPD-1 at week-4 of the study was predictive of surviving 3 or more years in patients treated with AIVITA’s immunotherapy, but not with the control article. Among patients treated with AIVITA’s immunotherapy, these sPD-1 criteria appropriately classified 80% of 3-year survivors, and 86% of patients who did not survive three years.

"These observations suggest that sPD-1 may be a useful biomarker for melanoma patients being treated with our platform immunotherapy, and/or to predict efficacy after only three injections," said Dr. Robert O. Dillman, Chief Medical Officer at AIVITA. "We look forward to confirming these results in larger studies and investigating whether it can predict response in other cancers."

AIVITA is currently conducting three clinical studies investigating its platform immunotherapy in patients with ovarian cancer, glioblastoma and melanoma. AIVITA uses 100% of proceeds from the sale of its ROOT of SKIN skincare line to support the treatment of women with ovarian cancer.

CLINICAL TRIAL DETAIL

OVARIAN CANCER

AIVITA’s ovarian Phase 2 double-blind study is active and enrolling approximately 99 patients who are being randomized in a 2:1 ratio to receive either the autologous cancer stem cell-targeting immunotherapy or autologous monocytes as a comparator.

Patients eligible for randomization and treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis from which sufficient monocytes were obtained, (4) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), and (5) who have completed primary therapy. The trial is not open to patients with recurrent ovarian cancer.

For additional information about AIVITA’s AVOVA-1 trial patients can visit: www.clinicaltrials.gov/ct2/show/NCT02033616

GLIOBLASTOMA

AIVITA’s glioblastoma Phase 2 single-arm study is active and is enrolling approximately 55 patients to receive the cancer stem cell-targeting immunotherapy.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a Karnofsky Performance Status of > 70 and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC). The trial is not open to patients with recurrent glioblastoma.

For additional information about AIVITA’s AV-GBM-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03400917

MELANOMA

AIVITA’s melanoma Phase 1B open-label, single-arm study will establish the safety of administering anti-PD1 monoclonal antibodies in combination with AIVITA’s cancer stem cell-targeting immunotherapy in patients with measurable metastatic melanoma. The study will also track efficacy of the treatment for the estimated 14 to 20 patients. This trial is not yet open for enrollment.

Patients eligible for treatment will be those (1) for whom a cell line has been established, (2) who have undergone leukapheresis from which sufficient monocytes were obtained, (3) have an ECOG performance grade of 0 or 1 (Karnofsky score of 70-100%), (4) who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations and (5) are about to initiate anti-PD1 monotherapy.

For additional information about AIVITA’s AV-MEL-1 trial please visit: www.clinicaltrials.gov/ct2/show/NCT03743298

On October 1, 2019 CTI BioPharma Corp. (Nasdaq: CTIC) reported that it has initiated patient enrollment in the PACIFICA pivotal Phase 3 trial of its investigational myelofibrosis treatment candidate, pacritinib (Press release, CTI BioPharma, OCT 1, 2019, View Source [SID1234551997]). The PACIFICA trial will compare the safety and efficacy of 200 mg of pacritinib administered twice daily (BID) to Physician’s Choice in 180 adult myelofibrosis patients with severe thrombocytopenia (platelet counts of less than 50,000 per microliter).

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"Initiation of the PACIFICA Phase 3 trial is an important step forward for the company and the pacritinib development program," said Adam R. Craig, M.D., Ph.D., President and Chief Executive Officer of CTI BioPharma. "An estimated one-third of patients with myelofibrosis are severely thrombocytopenic – a population with limited therapeutic options and poor survival, thereby making this disease setting a very important area of unmet medical need. Moving forward, successful trial execution is our primary focus, and with patient enrollment now underway, we expect to report topline results in mid-2021."

The PACIFICA trial is a randomized, active-comparator trial designed to evaluate the safety and efficacy of 200 mg of pacritinib administered twice daily (BID) compared to Physician’s Choice in 180 myelofibrosis patients with severe thrombocytopenia (platelet counts of less than 50,000 per microliter). Patients will be randomized in a ratio of 2:1 between pacritinib and Physician’s Choice, which may include steroids, thalidomide or lenolidamide, hydroxyurea or low-dose ruxolitinib. The primary endpoint of the trial is the percentage of patients who achieve at least 35% reduction in spleen volume at 24 weeks. Dr. Srdam Verstovsek, Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and Dr. John Mascarenhas, Associate Professor of Medicine Myeloproliferative Disorders Program, Tisch Cancer Institute, Mount Sinai School of Medicine, will be co-principal investigators in the PACIFICA trial. Professor Claire

Harrison, Professor of Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, will chair the trial’s Steering Committee.

The PACIFICA trial initiation follows the Type B, End-of-Phase-2a meeting with the U.S. Food and Drug Administration ("FDA" or "the Agency") held in July 2019 and the FDA’s acceptance of an amendment to the company’s PAC203 trial protocol, which has enabled a rapid transition to the PACIFICA Phase 3 trial. Results from the randomized, open-label Phase 2 PAC203 dose-finding trial are expected to be presented at a scientific conference before the end of 2019. For more information on the PACIFICA Phase 3 trial, please go to
PACIFICA-trial.com.

The company’s previously conducted Phase 3 PERSIST program consisted of the PERSIST-1 trial, which included a broad set of patients without limitations on platelet counts, and the PERSIST-2 trial, which was conducted in patients with low platelet counts. An ad-hoc analysis of pooled data from PERSIST-1 and PERSIST-2 evaluated results from patients with platelet counts of less than 50,000 per microliter and showed that 23% (n=104) of patients administered pacritinib had a ≥35% spleen volume reduction (SVR), compared to 2% (n=48) (p=0.0007) given the best available therapy, which in the PERSIST-1 trial excluded JAK2 inhibitors and in the PERSIST-2 trial included the approved JAK2 inhibitor, ruxolitinib. The most common treatment-emergent adverse events of any grade occurring in 20% or more of patients treated with pacritinib within 24 weeks during the PERSIST-1 and PERSIST-2 trials were gastrointestinal (generally manageable diarrhea, nausea and vomiting) and hematologic (anemia and thrombocytopenia).

About Myelofibrosis and Severe Thrombocytopenia
Myelofibrosis is a type of bone marrow cancer that results in formation of fibrous scar tissue and can lead to severe anemia, weakness, fatigue and an enlarged spleen and liver. Patients with severe thrombocytopenia are estimated to make up more than one-third of patients treated for myelofibrosis, or approximately 18,000 people.1 Severe thrombocytopenia, defined as blood platelet counts of less than 50,000 per microliter, has been shown to result in overall survival rates of just 15 months.2 Thrombocytopenia in patients with myelofibrosis is associated with the underlying disease but has also been shown to correlate with treatment with ruxolitinib, which can lead to dose reductions, and as a result, may potentially reduce clinical benefit. Survival in patients who have discontinued ruxolitinib therapy is further compromised, with an average overall survival of seven to 14 months.3,4 There are

currently no approved therapies available to treat myelofibrosis patients with severe thrombocytopenia, or patients who have failed ruxolitinib treatment, thereby making this a significant unmet medical need.

About Pacritinib
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and chronic lymphocytic leukemia (CLL), due to its inhibition of c-fms, IRAK1, JAK2 and FLT3.

On October 1, 2019 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on allogeneic gene-edited CAR T-cells (UCART), and Lonza (SWX: LONN), reported that the companies have entered into a manufacturing service agreement covering clinical manufacturing of Cellectis’ allogeneic UCART product candidates targeting hematological malignancies (Press release, Cellectis, OCT 1, 2019, View Source [SID1234550314]). Lonza is in charge of implementing Cellectis’ manufacturing processes as per current Good Manufacturing Practices (cGMP) in a way that meets the highest quality and safety standards outlined by the FDA. The manufacturing will take place at Lonza’s GMP facility in Geleen, Netherlands.

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William Monteith, Executive Vice President, Technical Operations, Cellectis:
"Working with Lonza, a world-class solutions provider with deep experience in the biotech and pharma industries increases our global capabilities and allows Cellectis to further strengthen its manufacturing expertise. This agreement not only bolsters our product supply for clinical trials, but it ensures that we are producing first-rate product candidates so that we can potentially deliver new hope to patients living with certain blood cancers."

Alberto Santagostino, Senior Vice President, Head of Cell & Gene Technologies, Lonza:
"Early-stage innovators with great science, like Cellectis, can find an ideal partner in Lonza as we bring great value in technical development and manufacturing, industrializing processes and enabling the journey to commercialization. We will draw on the experience at our cell and gene therapy center of excellence in the Netherlands, ideally equipped to support Cellectis in bringing their promising pipeline of allogeneic CAR-T therapies to people around the world in need of life-saving products."

Lonza’s supply will complement Cellectis’ ongoing collaboration and in-house manufacturing sites, IMPACT and SMART, which are currently under construction.

The manufacturing process of Cellectis’ allogeneic CAR T-cell product line, Universal CARTs or UCARTs, yields frozen, off-the-shelf, non-alloreactive engineered CAR T-cells. UCARTs are intended to be readily available CAR T-cells for a large patient population. Their production is industrialized with defined pharmaceutical release criteria.

On October 1, 2019 Ryvu Therapeutics and Selvita (WSE: SLV) reported that the National Court Register of Poland ("KRS") has recognized the corporate split of the Selvita parent company into two distinct organizations (Press release, Ryvu Therapeutics, OCT 1, 2019, View Source [SID1234542463]). The recognition by the court follows the Sept. 19, 2019, shareholder resolution to separate oncology therapeutics and contract research (CRO) business units.

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Going forward, Ryvu Therapeutics and Selvita (CRO) will now operate independently with separate executive management teams as well as supervisory boards, in accordance with the shareholder resolution.

Public trading of Ryvu Therapeutics under the symbol RVU, separated from Selvita is expected to begin on or about 9th October, subject to approvals from the National Depository for Securities ("KDPW") and the Warsaw Stock Exchange ("GPW").

Until this time, the value of the two independent companies will be reflected under the current listing of Selvita on the Warsaw Stock exchange.

Public listing of the contract research organization Selvita (CRO) under the symbol SLV is also expected on or about 16th October.