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

On April 19, 2023, the Company reported to have entered into an Asset Purchase Agreement (the "Purchase Agreement") with Blue Water Vaccines Inc. (the "Purchaser"). Pursuant to, and subject to the terms and conditions of, the Purchase Agreement, the Purchaser purchased substantially all of the assets related to the Company’s ENTADFI business (Filing, Veru, APR 19, 2023, View Source [SID1234630360]). The transaction closed on April 19, 2023. The purchase price for the transaction was $20.0 million, consisting of $6.0 million paid at closing, an additional $4.0 million the Purchaser is obligated to pay the Company in the Company’s fiscal year 2023 and an additional $10 million the Purchaser is obligated to pay the Company in installments in the Company’s fiscal year 2024, plus up to an additional $80 million based on the Purchaser’s net sales from ENTADFI business after closing (the "Milestone Payments "). The Milestone Payments are payable as follows: (1) $10 million is payable if annual net sales from the ENTADFI business are $100 million or more, (2) $20 million is payable if annual net sales from the ENTADFI business are $200 million or more and (3) $50 million is payable if annual net sales from the ENTADFI business are $500 million or more. No more than one Milestone Payment shall be made for the achievement of each net sales milestone. There can be no assurance that the net sales milestones for payment of any of the Milestone Payments will be reached.

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Furthermore, in connection with the transaction, the Purchaser assumed royalty and milestone obligations from the Company under an asset purchase agreement relating to the Company’s acquisition of the tadalafil-finasteride combination, which include a 6% royalty on all sales of tadalafil-finasteride and sales milestone payments of up to $22.5 million.

The Company and the Purchaser made customary representations and warranties, and agreed to certain customary covenants, in the Purchase Agreement. Subject to certain exceptions and limitations, each party has agreed to indemnify the other for breaches of representations, warranties and covenants and for certain other matters.

The description of the Purchase Agreement set forth herein is qualified in its entirety by reference to the full text of the Purchase Agreement, a copy of which is attached as Exhibit 10.1 hereto and incorporated by reference herein.

On April 20, 2023 Guardant Health, Inc. (Nasdaq: GH), a leading precision oncology company, reported it will report financial results for the first quarter of 2023 after market close on Tuesday, May 9, 2023 (Press release, Guardant Health, APR 19, 2023, View Source [SID1234630351]). Company management will be webcasting a corresponding conference call beginning at 1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time.

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Live audio of the webcast will be available on the "Investors" section of the company website at: www.guardanthealth.com. The webcast will be archived and available for replay after the event.