On April 19, 2023 Oxford BioTherapeutics Ltd. (OBT), a clinical stage oncology company with a pipeline of immuno-oncology and antibody-drug conjugate (ADC)-based therapies, reported entered into a collaboration with Groupe d’Oncologie Radiothérapie Tête Et Cou (GORTEC), an established, internationally renowned, European oncology and radiotherapy consortium specialising in clinical and laboratory research specifically for the benefit of head and neck cancer patients, to undertake a new Phase 1b trial investigating OBT’s lead asset, OBT076, in patients with Adenoid Cystic Carcinoma (ACC) (Press release, Oxford BioTherapeutics, APR 19, 2023, View Source [SID1234656437]).

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ACC is a rare, aggressive type of cancer which represents 2% of head and neck cancers and about 20% of salivary gland malignancies. Patients with ACC typically have a poor prognosis with a high risk of recurrence and metastasis. The Median survival of patients with ACC and distant metastasis is less than three years. There are no effective and/or standardized treatments available to date, beyond surgery and radiotherapy, for ACC cancer patients.

OBT has observed the drug receptor CD205, a unique characteristic for this disease, in at least 80% of ACC patients. CD205 is the target for OBT’s innovative ADC, OBT076, suggesting that OBT076 may have high therapeutic potential in this type of cancer.

Led by Professor Jean Bourhis, MD, PhD, Chief of Radiation Oncology at Lausanne University Hospital & Chairman at GORTEC, the trial will be carried out in patients with recurrent or metastatic ACC of the head and neck across the GORTEC network in France, Belgium and Switzerland, from an anticipated 15 study sites. It will investigate OBT076 both as a monotherapy and in combination with Agenus Inc. proprietary checkpoint inhibitor (CPI), balstilimab. Balstilimab is a PD-1 blocking antibody that has been studied in over 750 patients and is currently in clinical development in multiple solid tumor indications.

Prof. Jean Bourhis, said: "OBT076’s ability to target a highly prevalent receptor in ACC, and the potential to work in combination with checkpoint inhibitor therapies make it an interesting prospect as we continue seeking effective treatment options for patients with ACC. We are looking forward to leveraging our network for the trial and learning more about the drug’s potential in this rare indication with very limited treatment options."

OBT076 is currently being evaluated in Phase 1 clinical trials in the US and Europe across several advanced solid tumor indications, including gastric, endometrial, ovarian and non-small cell lung (NSCLC) cancer. Trial arms are investigating OBT076 both as a monotherapy and in combination with a CPI in these tumors. In preliminary data, OBT076 showed signs of clinical activity as a single agent and in combination with a CPI, including near complete responses after 2-5 cycles of OBT076 and 1-2 cycles of a CPI, in two chemo-refractory patients with low PD-L1 expression.

Christian Rohlff, PhD, Chief Executive Officer of Oxford BioTherapeutics, added: "We are excited to be collaborating with GORTEC to investigate OBT076 in another key indication where CD205 expression appears to be a driving factor. This collaboration will allow OBT to work in partnership with a number of world renowned experts in the field of head and neck cancer, who have a strong track record of conducting multiple, globally significant clinical trials in this field. We are hopeful that this trial will provide evidence to develop better treatment options for ACC patients while simultaneously adding to the growing body of data supporting OBT076’s potential both as an ADC monotherapy and as an immune primer to boost the effectiveness of CPI immunotherapies, particularly in patients with advanced and/or refractory tumors and those with low PD-L1 expression. As ACC is an orphan disease, should OBT076 be found to be effective, the regulatory process could be expedited via fast-track approval, given the high unmet medical need for this patient population."

On February 15, 2023 Biotechnology company Maxion Therapeutics (‘Maxion’) reported it has been awarded a prestigious GBP £2 million grant from Innovate UK, as part of its Biomedical Catalyst 2022 Round 2: Industry-led R&D funding competition (Press release, Maxion Therapeutics, APR 19, 2023, View Source [SID1234646398]). The funds will support the use of Maxion’s proprietary KnotBody platform to develop antibodies to treat autoimmune diseases (AID) with high unmet clinical need. The funding, which originates from UK Research and Innovation, is part of a GBP £25 million investment in projects to support UK-registered businesses to develop innovative solutions to address significant health or healthcare challenges.

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The funding follows Maxion’s announcement in February 2023 that it had completed a £13 million Series A financing, led by LifeArc Ventures, including Monograph Capital and BGF as equal participants.

The effective treatment of AID remains an important medical challenge and a significant area of unmet medical need. Currently, 4% of the world’s population, or around 300 million people, are thought to be suffering from over 80 different autoimmune conditions. In the UK alone, 4 million people live with an autoimmune condition, with the incidence increasing by 3-9% annually.

Antibody-based therapies have transformed the way chronic conditions like autoimmune disorders (AID) are treated, providing enhanced efficacy and safety while reducing the need for frequent administration. However, despite the success of current antibody therapies such as Humira, (the world’s best-selling drug), a significant proportion of patients do not respond well to treatment. Moreover, these therapies can lead to broad immunosuppression, increasing the risk of infections. As such, novel treatments are required that can offer broader patient coverage while minimising adverse effects.

Several ion channels are implicated in the pathogenesis of AID, but these critical cell surface proteins are seen as a complex target class for antibodies, with no antibody-based drugs targeting ion channels currently approved or in clinical development. At Maxion, nature has provided the answer in the form of "miniproteins" (knottins) that block ion channels. When knottins are fused onto the surface of antibodies, the resulting "KnotBodies" combine the ion channel-blocking activity of knottins with the excellent drug properties of antibodies, including long half-life in the body and the ability to further engineer their properties. This innovative molecular fusion approach serves as the foundation for Maxion’s patented KnotBody platform technology.

The company’s early R&D efforts have yielded KnotBodies to ion channel targets involved in AID, which will be further developed as selective and long-acting first-in-class and best-in-class therapeutics using Innovate UK funding.

Dr John McCafferty, CEO and co-founder of Maxion Therapeutics, said:
We are delighted to receive this substantial award from Innovate UK, to support the use of our KnotBody technology to develop therapeutics against this important but challenging class of targets. Our ultimate goal is to significantly improve the quality of life of patients by preventing and treating devastating autoimmune conditions, through the expansion and optimisation of our innovative pipeline of candidate therapeutics.

Dr Aneesh Karatt Vellatt, CSO and co-founder of Maxion Therapeutics, said:
KnotBody technology overcomes many of the challenges presented by conventional antibody development techniques, with an ability to specifically target ion channels linked to chronic autoimmune diseases. We are excited by the potential therapeutic candidates in our pipeline, and this new funding from Innovate UK will allow us to expedite their development and progress the most promising drug candidate towards clinical trials.

On April 19, 2023 AprilBio, a biopharmaceutical development company, reported on the 19th that it had raised 15 billion won in funds through the issuance of convertible bonds (CB) (Press release, AprilBio, APR 19, 2023, View Source;idx=23 [SID1234643374]).

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April Bio plans to begin full-scale development of dual-target anticancer drug candidates based on the funds secured.

April Bio is developing APB-BS2, a dual-target antibody therapy, with the goal of treating intractable solid tumors such as triple-negative breast cancer.

The targets of APB-BS2 are CD73 and cytokines.

First, CD73 is an enzyme that helps produce adenosine, which is necessary for the development of the tumor microenvironment (TME), which acts as a ‘protective shield’ around the tumor. When APB-BS2 inhibits CD73, the development of the tumor microenvironment is inhibited, allowing immune cells and anticancer drugs to attack the tumor more effectively.

The second target, cytokines, is responsible for activating natural killer (NK) cells and T cells. It can enhance anti-tumor ability.

It is not known which cytokine APB-BS2 binds to.

An April Bio official said, "When APB-BS2 was administered in an animal model of colon cancer, it showed similar activity to the PD-L1 antibody, an immune checkpoint inhibitor." He added, "We plan to expand the test subjects to triple-negative breast cancer, pancreatic cancer, etc. in the future to prove the effect." "We are also recruiting relevant personnel," he said. Collaborative research between April Bio and other companies is also actively underway.

APB-R5, whose technology was exported to Yuhan Corporation in August last year, is also a dual-target antibody treatment.

It was designed to overcome the shortcomings of immune side effects seen in existing cytokine treatments.

This official said, "After confirming the intended half-life in the body in preclinical tests using mice, we are confirming the efficacy in a solid cancer model."

The plan is to complete preclinical trials for APB-BS2 and APB-R5 next year and then submit a global phase 1 clinical trial protocol (IND).

Kim Jin-taek, Executive Director of Finance (CFO), said, "We judged that raising funds after the stock price rose could be a burden to existing investors, and that CBs issued at high stock prices could put pressure on the company to repay in the future." "We decided to raise funds at a time when the stock price is undervalued," he said.

The total cash that April Bio has secured through this procurement is 80 billion won. Managing Director Kim added, "Considering that we spend 15 billion won per year on research and development, we will be able to focus on new drug development without financial burden for the next few years."

Jin Hong-guk, director in charge of corporate activities (IR), said, "Phase 1 clinical trials for two substances, APB-A1 and APB-R3, will be completed this year, and clinical trials for new candidate substances will begin next year." He added, "Clinical trials for various candidate substances are underway. "As development progresses, the market for April Bio will be reevaluated," he said.

On April 15, 2023, Biosyngen Pte Ltd (hereinafter as "Biosyngen") reported that the Company received IND approval for its second product in the pipeline, a T-cell redirection therapy for the treatment of EBV-positive lymphoma (Press release, BioSyngen, APR 19, 2023, View Source;c=View&a=index&aid=99 [SID1234631946]). A week prior to this, the IND application of the same therapy has just been approved by China NMPA.

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A few months earlier, the Company’s first product (BRG01) targeting relapsed/metastatic nasopharyngeal cancer has been granted IND approval by both the US FDA and China NMPA. Following this IND approval to initiate the phase I/II clinical trials, Biosyngen makes a significant first-step towards the goal to gaining marketing authorization in the US and China. Biosyngen, an innovative biopharmaceutical company, is now the first in the CGT industry to possess dual IND approval from above regulatory bodies for its two products.

At present, Biosyngen’s IND application filing to Health Sciences Authority (HSA) is under review. Within 2023, the Company made plans for other IND applications to carry out phase I/II clinical trials for other therapies such as lung cancer, liver cancer and digestive track cancers across key regions – Singapore, the US and China.

Biosyngen broad director & COO, Michelle Chen, "Currently, cell therapy is a key strategy in healthcare development in many countries, including Singapore, China and the US. It is commonly acknowledged that cell therapy will accelerate human’s efforts to better address unconquered diseases to fulfill unmet medical needs and therefore benefit patients around the world".

About EBV-positive Lymphoma

EBV, the first oncovirus identified, is a human herpesvirus and has infected ~95% of global population. It has been listed as Group 1 carcinogen ("Carcinogenic to humans") by World Health Organization (WHO) and proved to be associated with a range of diseases including nasopharyngeal cancer, EBV-positive gastric cancers, lymphoma and lymphoproliferative diseases. EBV is so markedly lymphotropic that, for those who suffer from impaired immune system, especially T cell function, EBV may even induce lymphoblastic malignancies. EBV reactivation was also observed in patients who received bone marrow transplantation and CD7 CAR-T cell therapy, who may even develop EBV positive lymphoma.

The therapy developed by Biosyngen is an engineered T cell therapy, also known as a type of adoptive immune cell therapy indicated for nasopharyngeal cancer and EBV-positive lymphoma. Patients’ T cells are isolated and genetically modified in a GMP-compliant facility to enhance their ability to recognize and attack specific antigens on cancer cells. The modified T cells are expanded ex vivo and infused back into the patient. The infused T cells would bind to specific antigen on the cancer cells to mediate tumor killing. The preliminary safety and efficacy of BRG01 Therapy have been demonstrated in data from exploratory clinical trials.

The scientific direction of Biosyngen is focused on targeting multiple solid tumors and hematological tumors. The company has independently developed a number of exclusive technical platforms specifically for cancer immunotherapy, including IDENTIFIER, SUPER-T and MSE-T. These platforms are designed for improved safety and efficacy, equipping the company with capabilities to overcome challenges in antigen identification, antibody TCR screening and identification of immune cell function.

On April 19, 2023 Exscientia plc (Nasdaq: EXAI) reported four presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, being held from April 14-19, 2023 in Orlando, FL (Press release, Exscientia, APR 19, 2023, View Source [SID1234630417]).

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"We’re excited to further validate Exscientia’s end-to-end approach of integrating outstanding science with cutting-edge AI-driven precision medicine and translational research capabilities," said Andrew Hopkins, D.Phil, founder and Chief Executive Officer of Exscientia. "The clinical and preclinical data showcased at AACR (Free AACR Whitepaper) demonstrate how our approaches help not only efficiently design novel molecules, but also aim to differentiate them through superior properties and targeting the right patients to benefit from them. We look forward to continuing to develop our personalised medicine candidates with the goal of providing solutions to patients in need of effective treatment around the world."

Poster Presentations

Title: Identification of transcript adenosine fingerprint to enrich for A2AR and PD-1 inhibition responders
Session Title: Biomarkers of Therapeutic Benefit 2
Abstract Number: #2151
Date/Time: Monday, April 17 / 9:00 AM – 12:30 PM EST
●In this poster, Exscientia reveals its internally and preclinically developed adenosine burden score (ABS; first revealed at the end of 2022) is based on B-cell biology and that EXS21546 (‘546), Exscientia’s selective clinical stage A2AR antagonist, reverts effects of adenosine analogues ex vivo in patient tissue samples and other complex models
●Leveraging proprietary data, it was determined that the ABS is inversely correlated with PD-1 expression pathways as well as published PD-1 enrichment scores. Analysis of public human and mouse data confirms an enrichment of ABS-high samples are among those less likely to respond to checkpoint inhibition
●Current modelling in complex human blood samples shows that ‘546 as well as an example dual A2AR and A2BR antagonist are both highly correlated in reversing effects of adenosine analogue ex vivo
Title: Characterizing antitumor responses to EXS74539, a novel, reversible LSD1 inhibitor with potential in small-cell lung cancer

Session Title: Epigenetics
Abstract Number: #6290
Date/Time: Wednesday, April 19 / 9:00 AM – 12:30 PM EST
●Exscientia precision-designed EXS74539 (‘539), an LSD1 inhibitor with a differentiated profile combining reversibility and brain penetrance, to optimally target LSD1 in future oncology and haematology patient populations, including small-cell lung cancer (SCLC)
●The reversible mechanism-of-action combined with a shorter half-life may provide an opportunity to better manage on-target dose-limiting thrombocytopenia observed with other LSD1 inhibitors in development
●In vitro sensitivity analysis of small cell lung cancer (SCLC) cell line models to ‘539 alone was shown to not sufficiently predict in vivo response; researchers believe that predicting in vivo tumour response to ‘539 is critical to ensuring optimal use of the compound. Combining transcriptional and functional responses in vitro, however, may overcome this
●Exscientia has identified genetic fingerprints which may function as markers of ‘539 sensitivity, which are undergoing characterisation and validation in human SCLC patient samples

Title: Discovering novel targetable pathways by combining functional and multi-omic data from primary ovarian cancer samples
Session Title: Novel Targets and Pathways
Abstract Number: #4956
Date/Time: Sunday, April 16 / 1:30 PM – 5:00 PM EST
●This poster highlights the use of data generated with Exscientia’s precision medicine platform in combination with its proprietary methodology for multi-omics and multi-modal dataset mapping. By better understanding disease function, these tools combined can be leveraged to improve patient outcomes by uncovering clinically relevant targets at the discovery stage
●Data collected from disease-relevant patient samples including single cell functional responses, transcriptomics, protein-protein interactions and known drug-to-target interaction landscapes are combined with the goal of understanding cancer targets in the context of known biology, thereby understanding the target’s function and relevance early on in development, instead of relying on single endpoints common in the industry
●By mapping single cell functional and multi-omics data at baseline and after perturbation of a complex primary model system, researchers uncovered the PI3K/AKT/mTOR pathway as a novel anticancer node in high grade serous ovarian cancer (HGSOC). The poster further defines tumour necrosis factor (TNF) induced apoptosis function of the nuclear factor kappa B (NF-кB) pathway via TRAIL (TNF-related apoptosis-inducing ligand) as a promising focus area for HGSOC
Title: Data from first-in-human study of EXS21546, an A2A receptor antagonist, now progressing into Phase 1/2 in RCC/NSCLC

Session Title: Phase I Clinical Trials in Progress
Abstract Number: #CT114
Date/Time: Monday, April 17 / 1:30 PM – 5:00 PM EST
●‘546 is the first AI-designed immuno-oncology candidate in the clinic. Phase 1 objectives were achieved in a healthy volunteer study, confirming pharmacokinetics, pharmacodynamics, safety, and tolerability of ‘546, allowing selection of a starting dose for the ongoing IGNITE Phase 1/2 study in combination with a PD-1 inhibitor in patients with relapsed/refractory renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC)
●The poster highlights the IGNITE trial design, which is based on extensive simulations to enable the most efficient continuous reassessment method settings to predict and most accurately evaluate the anti-tumoural effect of ‘546 in combination with checkpoint inhibition as well as any dose limiting toxicity
●The IGNITE trial will also provide clinical data to support Exscientia’s patient enrichment biomarker strategy, using the ABS to identify patients with adenosine rich tumour microenvironments who may benefit from treatment. The first patient is expected to be enrolled in the first half of 2023