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 Chiome Bioscience Inc. reported that new contract with additional institutes had been finalized and the first patient has been dosed CBA-1205, the first-in-class antibody, in the second part (expansion part) of Phase I study(Press release, Chiome Bioscience, JUN 13, 2022, View Source jp/xcontents/45830/87891347/f845/469b/96ae/2719ff6df264/20220613150323815s.pdf [SID1234625710]).

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In the first part of Phase I study, CBA-1205 exhibited good safety and tolerability. In the second part, two doses will be given to the patients with hepatocellular carcinoma to evaluate safety and to determine the optimum dose for further development. Also, the exploratory efficacy and pharmacokinetics will be investigated.

The study will be conducted at National Cancer Center Hospital, National Cancer Center Hospital East. Additional institutes will be at Kanagawa Cancer Center and Niigata University Medical and Dental Hospital.

We hope that CBA-1205 exhibits good safety and efficacy profile in the second part that is key for early licensing deal. We will announce the progress in a timely manner.

There is no impact on the financial performance in the fiscal period ending December 31, 2022.

＜About CBA-1205＞

CBA-1205 is a humanized IgG1 afucosylated monoclonal antibody targeting cell surface antigen "DLK-1 (Delta-like 1 homolog)" which expresses on hapatocellular carcinoma and other solid cancers. CBA-1205 exhibits potent and specific anti-tumor activity in various DLK1 expressing cancer models by increasing ADCC (antibody-dependent cellular cytotoxicity). DLK-1 is known to control the proliferation and differentiation of stem cells, progenitor cells,
and other immature cells. CBA-1205 is expected to offer a new therapeutic option for the treatment of DLK-1 expressing cancer such as hepatocellular carcinoma. The present phase I clinical study is the first trial all over the world and CBA-1205 exhibited safety and tolerability.

On June 13, 2022 Sirona Biochem Corp. (TSX-V: SBM) (FSE: ZSB) (OTC: SRBCF) ("Sirona") reported it has entered into a global exclusive licensing agreement with Allergan Aesthetics, an AbbVie company (NYSE: ABBV), pursuant to which Allergan Aesthetics will develop and commercialize topical skin care treatments based on active ingredients derived from certain of Sirona’s patents for TFC-1067 and related family of compounds (Press release, Sirona Biochem, JUN 13, 2022, View Source [SID1234615935]).

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"We are very pleased to have finalized terms with a global leader in medical aesthetics and the innovator behind SkinMedica, a leader in the science of skin rejuvenation," said Dr. Howard Verrico, CEO of Sirona Biochem. "Our most recent clinical trial of TFC-1067 was a collaborative effort with Allergan Aesthetics to demonstrate the clinical potential in topical skin care treatments. This further validates our platform technology as viable for additional commercial products which we are actively pursuing. We would like to thank Dr. Linda Pullan of Pullan Consulting who assisted with our current success."

"Allergan Aesthetics’ global presence in the aesthetic space and goal to further enhance aesthetic medicine combined with Sirona’s disruptive technology made this all possible," reports Dr. Linda Pullan, of Pullan Consulting.

Under the license agreement, Sirona will a receive an upfront payment and further payments on achievement of milestones and royalties on product sales and has also agreed to financial terms as a supplier of its compounds.

On June 13, 2022 Oxford BioTherapeutics (OBT), a clinical stage oncology company with a pipeline of immuno-oncology and Antibody Drug Conjugate (ADC)-based therapies, reported a multi-year collaboration to research, develop and commercialize novel, first-in-class ADCs with ImmunoGen (IMGN), a leader in the expanding field of ADCs for the treatment of cancer (Press release, Oxford BioTherapeutics, JUN 13, 2022, View Source [SID1234615951]). The companies will utilize ImmunoGen’s linker-payload technology directed to novel targets identified via OBT’s proprietary OGAP discovery platform. The companies will support these R&D efforts through joint funding and by combining their respective proprietary technologies.

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"I am very enthusiastic about our new partnership with ImmunoGen, a leader in the development of ADCs," said Christian Rohlff, PhD, Chief Executive Officer (CEO) of Oxford BioTherapeutics. "The company’s expertise, in combination with the unique targets from our OGAP database, provides potential to strengthen our respective drug pipelines with novel and highly differentiated ADCs for cancer patients in need of novel therapeutic options."

As part of the agreement, OBT will receive an upfront payment from ImmunoGen, reflecting OBT’s preclinical programs to be included in the partnership.

In addition, once antibodies generated by OBT have been coupled with ImmunoGen’s proprietary linker-payload technology, each company will have the opportunity to select one or more development programs to further develop on its own.

Each company is eligible to receive milestone payments based on the achievement of pre-specified development, regulatory, and commercial milestones, as well as tiered royalties as a percentage of worldwide commercial sales, with respect to each program selected by the other company. Once a company has chosen a given program, it will be solely responsible for all R&D costs associated with the specific program.

"OBT has demonstrated expertise in identifying novel targets for the development of specific antibodies – two key components to generating successful ADCs," said Stacy Coen, ImmunoGen’s Senior Vice President and Chief Business Officer. "This expertise, combined with ImmunoGen’s portfolio of cancer-killing payloads and linkers, will be instrumental as both companies work to develop novel ADCs designed to address cancers with high unmet need. We look forward to working with OBT as we expand and diversify our investment in ADC research capabilities, deepen our pipeline, and transition to a fully-integrated oncology company."

ImmunoGen’s portfolio is comprised of next-generation maytansinoid, DNA-acting, and novel camptothecin toxins and proprietary linkers. This collaboration will utilize novel targets identified by OBT combined with ImmunoGen’s proprietary toxins and associated linkers. OBT has clinical experience with ImmunoGen’s ADC platform and DM4 payload, which is utilized in OBT’s lead program OBT076, an ADC currently in clinical trials as a monotherapy, as well as in combination with checkpoint inhibitors, in patients with advanced or refractory solid tumors, including gastric, bladder, ovarian, and lung cancer.

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.