On June 13, 2022 BlueSphere Bio, a T-cell receptor (TCR) T-cell therapy company developing a powerful TCR discovery platform and novel therapeutic candidates for patients with hematologic malignancies and solid tumors, reported that David Apelian, M.D., Ph.D., MBA, Chief Executive Officer of BlueSphere Bio, will provide a corporate overview at the 2022 BIO International convention on June 13, 2022 at 3:45 p.m. PT in company presentation theater 2 (Press release, BlueSphere Bio, JUN 13, 2022, View Source [SID1234616066]).

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The presentation will highlight the company’s latest data supporting future clinical development of their adoptive TCR T-cell therapies and novel high-throughput TCXpress and NEOXpress platforms designed to target some of the most challenging cancers. The TCXpress platform has enabled the discovery of BlueSphere’s first clinical candidate, a TCR T-cell therapy directed against the minor histocompatibility antigen (miHA) HA-1. The company anticipates filing its first IND by the end of 2022. The TCXpress platform has also enabled the discovery of four new TCRs reactive against other relevant miHAs, in addition to HA-1. BlueSphere plans to announce details on these other targets later this year.

BlueSphere’s management will be available to participate in one-on-one meetings with industry executives and investors registered for the conference. To schedule a meeting with the Company, please reach out through the BIO partnering system.

On June 13, 2022 Hamlet Pharma reported that signed a joint development agreement with Neurochase Limited, founded by Professor Steven Gill, a world leading expert in the area of neurosurgery, to develop novel technology and methods to treat Central Nervous System (CNS) tumors with Alpha1H (Press release, HAMLET Pharma, JUN 13, 2022, View Source;utm_medium=rss&utm_campaign=brain-tumor-therapy-a-new-indication-for-hamlet-pharma [SID1234615967]).

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Alpha1H is effective against a range of solid and haematological tumor cells that commonly metastasize to the CNS. Early studies in rats have shown that infusion of HAMLET into the brain markedly delayed the progression of glioblastomas. Glioblastomas are highly invasive and malignant brain tumours with a poor prognosis, accounting for about 60% of all primary brain tumors. At the time of diagnosis, the tumors are mostly inaccessible to complete surgical removal due to spread of tumor cells from the primary tumor site and there is a lack if efficient, alternative treatments.

As a pioneer in this field, Professor Gill has invented new technologies for drug delivery into the brain and used them successfully in the treatment of neurological diseases and cancers. In this collaboration between Neurochase and Hamlet Pharma, new technology will be developed for delivery of Alpha1H to the leptomeninges for treatment of primary and secondary CNS tumors. The collaboration will primarily explore infusion of Alpha1H in an animal model in preparation for clinical trials.

Steven Gill said "We are delighted to be collaborating with Hamlet Pharma on this programme. Alpha 1H has shown very promising results to date as a potential treatment for CNS tumors. I am hopeful that by working together we can improve the otherwise poor outcome for patients with CNS tumors".

" Combining this novel technology with Alpha1H to explore the treatment of brain tumors is a very exiting prospect", says Catharina Svanborg, Professor and Chairman of Hamlet Pharma AB.

On June 13, 2022 Exscientia plc (Nasdaq: EXAI) reported data from its Phase 1 healthy volunteer study of EXS-21546, its highly selective A2A receptor antagonist ​​co-invented and developed through a collaboration between Exscientia and Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; Nasdaq: EVO) (Press release, Evotec, JUN 13, 2022, View Source [SID1234615966]). Topline data from this healthy volunteer study confirmed Exscientia’s target product profile design, including potency, high receptor selectivity and expected low brain exposure with no CNS adverse events reported, supporting advancement of EXS-21546 to a Phase 1b/2 study in patients with solid tumours exhibiting high adenosine signatures.

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​​"Topline data from our phase 1a study of EXS-21546 demonstrate the ability of our AI-based platform to create novel molecules based upon defined design objectives and with a high level of translatability to human biology. EXS-21546 is a pilot programme from the early days of our platform, and we are proud that it achieved our targeted objectives of potency, selectivity and pharmacokinetics," said David Hallett, Ph.D., Chief Operating Officer and head of drug discovery for Exscientia. "Moving forward, a primary challenge in clinical development of an A2AR antagonist is identifying patients who will benefit the most from this type of immunomodulatory therapy. We believe that utilising our unique precision medicine platform to analyse patient tumour microenvironments ex vivo, including immune function, will help us identify the right patients for our drug."

The EXS-21546 phase 1a study was a three-part dose-finding trial evaluating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses (SAD) and multiple ascending doses (MAD) of EXS-21546. The study randomised 60 healthy male subjects across all three parts. One of the study’s primary goals was to inform the optimal starting dose for EXS-21546 for the Phase 1b/2 study in cancer patients.

The study showed that observed human PK for EXS-21546 was in line with what had been designed for and predicted in preclinical modeling, supporting a twice-daily (BID) dose for continuous A2A receptor inhibition over a dosing interval.

EXS-21546 showed dose-dependent inhibition of CREB phosphorylation in CD8-positive cells, with the PD profile mirroring plasma exposure. Inhibition of A2A receptor signaling was sustained over the BID dosing period, demonstrating a level of lasting target engagement.

EXS-21546 was well-tolerated with no CNS adverse events reported in the SAD portion at all doses (30mg, 90mg, 250mg, 400mg) and in the MAD portion at 150mg BID. In the MAD phase, a lab abnormality of elevated ALT and AST was observed in one subject that was classified as a Grade 3 Serious Adverse Event. This event was observed in one subject three days after completion of 14 days of treatment and resolved without medical intervention. The subject was asymptomatic during the treatment period and reported no adverse events while on drug.

Based on these results, Exscientia expects to initiate a Phase 1b/2 study of EXS-21546 in patients with high adenosine signature solid tumours in the second half of 2022. The Phase 1b/2 study is being designed to evaluate higher doses of EXS-21546.

The Company expects to share additional data from this Phase 1a study at future medical meetings.

About EXS-21546

EXS-21546, an AI-designed A2A receptor antagonist, was co-invented and developed by Exscientia and Evotec. Exscientia designed the compound leveraging its AI-driven platform and Evotec provided biology and chemistry capabilities.

Some tumours produce high levels of adenosine, which binds and activates A2A receptors on immune cells, resulting in the suppression of the anti-tumour activity of the immune system. EXS-21546 is being investigated for its ability to prevent high concentrations of adenosine from activating the A2A receptor, and thereby its potential to promote the anti-tumour activity of the immune cells.

About the EXS-21546 Phase 1a Trial

The Phase 1 study was a three-part study in male healthy volunteers to assess the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of EXS-21546. Part 1 was a randomised, double-blind, placebo-controlled, SAD study with a food effect assessment where 41 healthy volunteers were randomised 3:1 (in a ratio of 6 active to 2 placebo per cohort). Part 2 was a randomised, double-blind, placebo controlled, MAD study over 14 days. Part 2 was completed after the enrolment of 1 cohort (8 subjects) who received 150mg EXS-21546 BID. Part 3 was a 3-way crossover, open label, randomised study, where 11 subjects were enrolled to evaluate a capsule formulation (fed and fasted) as compared to an oral suspension (fasted) formulation.

On June 13, 2022 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) reported that the Company has entered a drug discovery collaboration with Janssen Pharmaceutica NV, one of the Janssen Pharmaceutical Companies of Johnson & Johnson ("Janssen") (Press release, Evotec, JUN 13, 2022, View Source [SID1234615954]). Evotec’s innovative TargetAlloMod platforms will be evaluated to discover first-in-class novel mode of action therapeutic candidates. The agreement was facilitated by Johnson & Johnson Innovation.

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Under the agreement, Evotec and Janssen will jointly conduct screens on the identified targets and collaborate with hit identification and lead optimisation of the most promising chemical assets, leveraging Evotec’s end-to-end integrated drug discovery and development platform.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "We are very proud to enter into this collaboration to explore unique approaches to high potential cell surface drug targets with novel therapeutic modalities and to deliver and make innovative therapeutic options available to patients."

Besides research funding, Evotec is entitled to success-based research and commercial milestones up to approximately € 210 m per project as well as tiered royalties on products resulting from this collaboration.

About TargetAlloMod
Scientists at Evotec have discovered that for certain extracellular receptors, small molecules can bind allosterically and induce a natural proteolytic cleavage process to shed the ectodomain. This results in the disruption of cell signalling and the shed ectodomain can, in many cases, further act as a sink for the native ligand of the targeted receptor. The TargetAlloMod platform comprises a suite of proprietary assay principles and computational tools to assess and screen extracellular receptor targets for shedding and the induction of shedding by small molecule allosteric modulators. This platform has broad applicability across many therapeutic areas.

On June 13, 2022 Pfizer Inc. (NASDAQ:PFE), MorphoSys U.S. Inc., a fully owned subsidiary of MorphoSys AG (FSE: MOR; NASDAQ:MOR), and Incyte (NASDAQ:INCY) reported that a clinical trial collaboration and supply agreement to investigate the immunotherapeutic combination of Pfizer’s TTI-622, a novel SIRPα-Fc fusion protein, and Monjuvi (tafasitamab-cxix) plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT) (Press release, MorphoSys, JUN 13, 2022, View Source [SID1234615926]).

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"TTI-622 blocks the signal-regulatory protein (SIRP)α–CD47 axis, which is a key checkpoint expected to become an important backbone immunotherapy across multiple tumors, especially hematological cancers," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "The early results for TTI-622 in late-line advanced lymphoid malignancies reflect the potential for class-leading monotherapy activity, and preclinical evidence with a diverse set of therapeutic agents provide a strong rationale for testing combination therapies. We are pleased to collaborate with MorphoSys and Incyte, generating additional evidence on the potential of TTI-622 to improve outcomes for patients with DLBCL."

‟Monjuvi in combination with lenalidomide is an important treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma, and its mechanism of action, efficacy and safety profile make it an attractive combination partner," said Malte Peters, M.D., MorphoSys Chief Research and Development Officer. "We believe that the addition of novel immunotherapies, such as the investigational anti-CD47 blocking agent TTI-622, to the backbone of Monjuvi plus lenalidomide have the potential to provide new meaningful combination treatment options for patients with relapsed or refractory diffuse large B-cell lymphoma."

‟This collaboration has the potential to advance patient care in an area where there continues to be significant unmet medical need," said Lance Leopold, M.D., Group Vice President, Clinical Development Hematology and Oncology at Incyte. "We are proud to support this research effort to evaluate the potential of a new chemotherapy-free combination for these patients."

Pfizer’s TTI-622 is currently in Phase 1b/2 development across several indications, with a focus on hematological malignancies. CD47 is an innate immune checkpoint that binds SIRPα and delivers a "don’t eat me" signal to suppress macrophage phagocytosis. Overexpression of CD47 in solid and hematological malignancies, including in DLBCL, is associated with poor prognosis.
Monjuvi (marketed ex-U.S. as Minjuvi), a CD19-directed immunotherapy, in combination with lenalidomide is a treatment for adult patients with relapsed or refractory DLBCL not otherwise specified, and who are not eligible for ASCT. In this indication, accelerated or conditional approvals were granted by the U.S. Food and Drug Administration, the European Medicines Agency and other regulatory authorities. Monjuvi is being co-commercialized by MorphoSys and Incyte in the United States. Incyte has exclusive commercialization rights outside the United States.

Preclinical data by Morphosys have shown a strong synergy of Monjuvi and anti-CD47 antibodies in in vitro and in vivo lymphoma models, providing scientific rationale for investigating this combination in clinical trials. This preclinical data was presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in 2020.
Under the terms of the agreement, Pfizer will initiate a multicenter, international Phase 1b/2 study of TTI-622 with Monjuvi and lenalidomide for patients with relapsed or refractory DLBCL who are not eligible for ASCT. MorphoSys and Incyte will provide Monjuvi for the study, which will be sponsored and funded by Pfizer and is planned to be conducted in North America, Europe and Asia-Pacific.
The collaboration is effective immediately upon the execution of the agreement.

About Tafasitamab

Tafasitamab is a humanized Fc-modified CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Monjuvi and Minjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name MONJUVI in the U.S., and marketed by Incyte under the brand name Minjuvi in Europe, the UK and Canada.

XmAb is a registered trademark of Xencor, Inc.