On April 18, 2023 TME Pharma N.V. (Euronext Growth Paris: ALTME) (Paris:ALTME), a biotechnology company focused on developing novel therapies for treatment of cancer by targeting the tumor microenvironment (TME), reported the successful closing of a financing of €2 million (Press release, TME Pharma, APR 18, 2023, View Source [SID1234630291]). The financing extends the company’s cash runway into December 2023, sufficient to reach its next major inflection points and to allow further advance its ongoing GLORIA Phase 1/2 clinical study of NOX-A12 combination therapies in newly diagnosed brain cancer (glioblastoma) patients.

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The transaction involves: 1) a €1 million equity financing at the price of €1.04161 per share from a group of new investors, 2) a drawdown of €1.08 million under agreement with Atlas Special Opportunities, LLC (ASO) by issuing 1,100 convertible bonds, 3) the conversion of €2 million (~48%) outstanding convertible bonds held by ASO into newly issued shares at a conversion price of €1.04161 per share, 4) a soft lock-up of all shares issued through this transaction for a 6-month period, and 5) a lock-up of all remaining convertible bonds for a 6-month period.

Moreover, the company will not draw any further tranches from the ASO convertible bond vehicle and the agreement with ASO is terminated other than with regard to already issued convertible bonds. TME Pharma is also studying options to be able to repurchase the remaining convertible bonds, as allowed under the agreement, to prevent conversion to shares.

"We are very pleased to announce the details of a successful transaction concluded with a group of new investors and Atlas, which extends our cash runway into December 2023," said Aram Mangasarian, CEO of TME Pharma. "This innovatively-structured transaction represents the first step in the commitment we made to our shareholders to end reliance of the company on convertible bond financing. By removing the pressure of convertible bonds, we hope our exceptional therapeutic assets will be able to reach a valuation on the market that reflects their therapeutic potential. We estimate the addressable market for first line glioblastoma to be $2.5 billion per year. We would like to thank Atlas for their support in facilitating the transaction and welcome our new investors who showed their confidence in TME Pharma through this latest financing. This will enable us to maintain our focus on our goal of developing novel therapies for cancer patients and bringing them to market."

The convertible bond agreement with ASO was initially entered on April 23, 2020, and amended on October 14, 2020, December 29, 2021, May 19, 2022, and April 17, 2023.

The characteristics, terms and conditions and dilution resulting from the transaction may be found in the Annex to this press release.

On April 18, 2023 MAIA Biotechnology, Inc. (NYSE American: MAIA) reported the peer-reviewed publication of original research article in this month’s issue of Molecular Cancer Therapeutics (volume 22, issue 4), a renowned American Association of Cancer Research (AACR) (Free AACR Whitepaper) journal that publishes translational research studies focused on the discovery and preclinical development of therapeutic agents for oncology (Press release, MAIA Biotechnology, APR 18, 2023, View Source [SID1234630290]). The preclinical study, entitled "Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma," showed highly potent anticancer activity of THIO in multiple HCC preclinical models.

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The study revealed the anti-tumor immune response role of THIO as a telomerase-dependent telomere targeting therapeutic in HCC models. THIO induces telomere damage and activates the cGAS-STING pathway, which is a major intracellular signaling pathway that plays a role in innate immune responses. THIO enhances the cross-priming capacity of dendritic cells (DCs), which are antigen presenting cells of the adaptive immune system and activates tumor specific T cells. Observed potent anticancer activity is taking place in CD8-positive T cell dependent manner. Moreover, the study showed a potential role of immunogenic protein molecule HMGB1 (high-mobility group box 1, which are released during cancer cell death), in THIO induced T cell activation. In addition, the study demonstrated enhanced efficacy and durability of complete tumor regression when THIO is followed by administration of immunotherapies (an anti-PD-1 or anti-PD-L1) and anti-VEGF (anti-vascular endothelial growth factor, one of the major anti-angiogenic drug target) in advanced, resistant HCC tumors providing a strong scientific rationale for a clinical trial in HCC.

"The knowledge gained from this study will help support our understanding of the compound’s mechanism of action and its broad therapeutic utility. Moreover, this publication strengthens our scientific rationale already included in our current clinical development plan for THIO-102, a Phase 2 clinical study in multiple solid tumor indications, including HCC," said MAIA’s Chief Scientific Officer Sergei Gryaznov, Ph.D.

"The findings from our study provides solid rationale for THIO to be evaluated as a treatment of liver cancer, as our Company already holds the US FDA Orphan Drug Designation for this clinical indication. This published evidence supports our strong belief that THIO, especially in combination with immune checkpoint inhibitors and other standard of care agents, may be clinically studied for treatment of various forms of cancer," added Vlad Vitoc, M.D., MAIA’s Chief Executive Officer.

The full results are available in Molecular Cancer Therapeutics and online here.

On April 18, 2023 Veneno Technologies Co. Ltd. is reported that the company has entered into a joint research agreement with Sumitomo Pharma Co. Ltd., headquartered in Osaka, Japan (Press release, Veneno Technologies, APR 18, 2023, View Source [SID1234630287]).

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"This is the second such research agreement with a major Japanese research company we have completed this month. We are particularly pleased to be working with researchers at Sumitomo Pharma Co. Ltd." said Kazunori Yoshikawa, President and CEO at Veneno Technologies Co. Ltd.

Under the terms of the agreement, Veneno Technologies [View Source will conduct a program to obtain functional peptides (DRPs) for ion channels targeted by Sumitomo Pharma using Veneno Technologies’ next-generation peptide discovery technology, the PERISS method (intra-periplasm secretion and selection). Work on this project is expected to begin during the 2nd Quarter, 2023.

For inquiries regarding this release, please contact:
Veneno Technologies Co. Ltd.
[email protected]

On April 18, 2023 Orum Therapeutics, a clinical-stage private biotechnology company pioneering cell-specific targeted protein degradation (TPD² ) and targeted protein stabilization (TPS² ), reported new preclinical data for three of Orum’s therapeutic programs: ORM-5029, which is a proprietary GSPT1 degrader conjugated to HER2-targeting antibody pertuzumab; ORM-6151, which delivers GSPT1 degrader to CD33+ tumors; and its new immuno-oncology program for a Cbl-b inhibitor (Cbl-bi) conjugated to anti-PD-1 antibody pembrolizumab (Press release, Orum Therapeutics, APR 18, 2023, View Source [SID1234630289]). The data were presented in three posters at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

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"We are pleased to present new data supporting clinical development of two programs from our TPD² GSPT1 Degrader Platform, which was developed to improve the therapeutic window and realize the full potential of GSPT1 degraders through precision delivery to cancer cells via antibody drug conjugates"

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"We are pleased to present new data supporting clinical development of two programs from our TPD² GSPT1 Degrader Platform, which was developed to improve the therapeutic window and realize the full potential of GSPT1 degraders through precision delivery to cancer cells via antibody drug conjugates," said Peter Park, Ph.D., Chief Scientific Officer of Orum Therapeutics. "We are also excited to unveil at AACR (Free AACR Whitepaper) our new TPS² platform, which has the potential to achieve the full promise of Cbl-b inhibitors through T cell-specific delivery. With this novel approach, we show that we can limit unwanted systemic exposure, including the risk of toxicity associated with c-Cbl inhibition, prolong the activation of exhausted PD-1+ T cells, and provide resistance to negative environmental cues such as TGF-β or regulatory T cells. We believe our approach of harnessing the power of protein degraders and stabilizers with the precision of antibody targeting will improve the treatment of cancer for more patients."

Details of the data presented are as follows:

Title: A novel antibody-enabled Dual-precision Targeted Protein Stabilization (TPS²) that augments anti-tumor immune response by targeting Cbl-b inhibitor to exhausted T cells while blocking checkpoint molecule, PD-1
Presenter: Joanne Lim, Ph.D.
Abstract Number: 4436
Summary: Cbl-b inhibition results in stabilization of intracellular proteins downstream of the T cell activation pathways. Using a murine model well-established to be refractory to anti-PD-1 antibody treatment, we demonstrated that anti-PD-1-Cbl-b inhibitor approach increased effector T cell markers in the tumor and delayed tumor growth.
Presented Data:

The delivery of Cbl-b inhibitor (Cbl-bi) conjugated to anti-PD-1 antibody enhances the saturating, maximum activation of anti-PD-1 antibody by 300% in PD-1/PD-L1 blockade assay.
Anti-PD-1-Cbl-bi conjugates enhance T cell responses of mixed lymphocyte reaction in a dose-dependent manner and overcome suppressive effects of TGF-β and Treg cells compared to antibody alone in vitro.
Anti-PD-1-Cbl-bi conjugates enhance ex vivo activation of tumor-associated T cells from human cancer patients compared to antibody alone or when treated with antibody and unconjugated Cbl-bi.
Anti-PD-1-Cbl-bi conjugates delay the growth of melanoma tumors in hPD-1 transgenic mice, with corresponding increase in intratumoral transcript levels of CD3e, granzyme B, and perforin in the tumor.
Title: ORM-6151: A first-in-class CD33-antibody enabled GSPT1 degrader for AML
Presenter: James Palacino, Ph.D.
Abstract Number: 2700
Summary: ORM-6151 shows robust single-dose efficacy, both in vitro and in vivo with superiority or comparability to standard of care (SOC) agents. In addition, in vitro testing demonstrated superior tolerability to healthy bone marrow progenitor cells, suggesting better tolerability. Responses in representative TP53 wild-type and mutant AML models demonstrated comparable activity, indicating the potential for responses in a large percentage of AML patients with poor treatment options.
Presented Data:

ORM-6151 shows robust in vitro activity in p53 wild-type and mutant cell models.
In ex-vivo AML blasts, ORM-6151 demonstrates efficacy superior to CC-90009, a small-molecule GSPT1 degrader, or Mylotarg, an FDA-approved treatment for AML.
Compared to CC-90009 or Mylotarg, ORM-6151 exhibits minimal cytotoxic activity to healthy hematopoietic progenitor cells in vitro.
A single treatment of ORM-6151 at 3 mg/kg regresses MV4-11 tumors in vivo mouse model with 9/9 complete response (CR), and a single dose of 1 mg/kg produced equivalent antitumor effect as SOC doublet given at optimal repeated dose.
Title: Development of RNAscope multiplex-based assay for exploratory pharmacodynamic biomarkers assessment in breast cancer patients from Phase I clinical trial of ORM-5029, a potent GSPT1 degrader
Presenter: Shikha Saini, Ph.D.
Abstract Number: 2118
Summary: To fulfill the need to develop pharmacodynamic biomarkers as predictors of efficacy to support clinical development of ORM-5029, Orum identified a novel GSPT1 antibody for detection of depletion following treatment with ORM-5029. GSPT1 depletion and subsequent activation of the integrated stress response are both seen following in vitro or in vivo treatment with ORM-5029. Degree of pharmacodynamic (PD) change correlates with depth and duration of in vivo response. Orum is currently developing a multiplexed (IF/ISH/ISH) assay to track PD responses in patients, with an aim to better predict responses and efficacious doses.
Presented Data:

Orum identified the depletion of GSPT1 as a target-proximal pharmacodynamic biomarker in ORM-5029 treated in vitro and in vivo samples.
Loss of GSPT1 drives activation of integrated stress response and upregulation of ATF3 and DDIT3 mRNA and these responses are also seen following treatment with ORM-5029, in both in vitro BT-474 cells and in vivo HCC1568 mouse model.
PD responses correlate with degree and duration of response in an in vivo model treated with ORM-5029.
The posters are available to download through the links below:
PD-1-Cbl-bi TPS² preclinical poster: View Source
ORM-6151 preclinical poster: View Source
ORM-5029 predictive biomarker poster: View Source

On April 18, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported initial data from its ongoing Phase 1/2 TRESR clinical trial evaluating camonsertib (RP-3500/RG6526, partnered with Roche), a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase), in combination with a poly (ADP-ribose) polymerase inhibitor (PARPi), talazoparib, and initial data from its ongoing Phase 1b/2 ATTACC clinical trial, evaluating camonsertib in combination with two additional PARPis, niraparib or olaparib, in patients with advanced solid tumors (Press release, Repare Therapeutics, APR 18, 2023, View Source [SID1234630288]).

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The data involving novel combinations of low doses of camonsertib and three different PARPis are featured today at the 2023 AACR (Free AACR Whitepaper) Annual Meeting in a clinical plenary session titled, "Safety and efficacy of three PARP inhibitors (PARPi) combined with the ataxia telangiectasia- and Rad3-related kinase inhibitor (ATRi) camonsertib in patients (pts) with solid tumors harboring DNA damage response (DDR) alterations" (abstract presentation number CT018). This study population comprised patients with a broad range of historically difficult to treat tumors, including patients with platinum-resistant tumors, patients who had either recurred or progressed during or after treatment with PARPis, and patients who had developed known BRCA-reversion mutations.

"We see promise in the camonsertib-PARPi combinations when administered concomitantly, at low doses across tumor types, especially in recurrent ovarian cancer given that nearly all had recurred after prior PARPi treatment. We are particularly encouraged by the depth of response and duration of treatment," said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "Dose optimization to refine the combinatorial dose in additional tumor-specific expansions beyond ovarian within our ATTACC study is ongoing as part of our collaboration with Roche."

"We previously established a promising safety and early efficacy profile of camonsertib as a monotherapy and this year’s data at AACR (Free AACR Whitepaper) further support camonsertib as a partner for combinational regimens and provides a clear rationale for further development of this compound," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "Notably, the circulating tumor DNA (ctDNA) data showed a strong correlation with the degree of tumor shrinkage and duration of disease control, and provide a mechanistic explanation for the observed durable clinical benefit in heavily pretreated patients, beyond the natural history of the disease. We look forward to refining our dose optimization efforts and efficacy assessment in tumor specific expansions. This data remains consistent with what we were anticipating at the time of entering our partnership with Roche and we are excited to continue this important clinical development together."

Key Initial Findings from the TRESR Phase 1/2 and ATTACC 1b/2 PARPi Combination Studies:

TRESR (NCT04497116) is a first-in-human, multi-center, open-label Phase 1/2 dose-escalation and expansion study, designed to establish the recommended Phase 2 dose and schedule, evaluate safety and pharmacokinetics and identify preliminary anti-tumor activity associated with camonsertib, given alone and in combination with talazoparib or in combination with gemcitabine.

ATTACC (NCT04972110) is a first-in-human, multi-center, open-label Phase 1b/2 dose-escalation and expansion study, designed to evaluate safety and pharmacokinetics and identify preliminary anti-tumor activity associated with camonsertib in combination with niraparib or olaparib.

The clinical plenary session described initial combination Phase 1/2 results from 107 patients, of which 90 patients were evaluable for efficacy treated at least 13 weeks prior to the data cutoff of February 27, 2023.

Key highlights from the data presented at the 2023 AACR (Free AACR Whitepaper) Annual Meeting include:

Camonsertib combination resulted in durable clinical benefit across tumor types and different genomic alterations, regardless of choice of PARPi and presence of platinum resistance. Overall clinical benefit rate (CBR) for all patients was 48%. Patients with platinum-resistant tumors had an overall response rate (ORR) of 12% and CBR of 49%, and benefited similarly to non-platinum-resistant tumors (ORR 13%, CBR 46%).
Compelling results were observed particularly in patients with advanced ovarian cancer (n = 19). In these patients, overall response was 32%, CBR was 58% and median progression-free survival (mPFS) was approximately 7 months with treatment >16 weeks and ongoing in 9 patients.
Early ctDNA molecular responses in 66% (31/47) of evaluable patients confirms antitumor activity of low dose, intermittent PARPi + ATRi therapy. The molecular response rate (MRR) was significantly higher in patients with clinical benefit (83%) compared to those without (48%; p=0.015), confirming treatment effect. Molecular responses were observed in patients with prior PARPi exposure (57%) and platinum resistance (64%).
Camonsertib combinations appear to be well tolerated. Dose limiting toxicity (DLTs) in 68 patients treated with the proposed combination doses were related to myelotoxicity only (Grade 3+ anemia 3%, thrombocytopenia 6%, neutropenia 7%, and febrile neutropenia 3%). No prophylactic growth factors were required when administering the PARPis at evaluated doses.
Additional relevant presentations at AACR (Free AACR Whitepaper):

Title: Characterization of CCNE1 amplifications and associated genomic features in ovarian and uterine cancers
Session: Biomarkers of Therapeutic Benefit 5, Tuesday April 18, 2023, 1:30 PM – 5:00 PM
Abstract Number: 5469

Title: Tumor heterogeneity of CCNE1 copy number assessed by fluorescence in situ hybridization (FISH) in ovarian and uterine cancers and correlation with cyclin E protein expression
Session: Biomarkers of Therapeutic Benefit 2, Monday April 17, 2023, 9:00 AM – 12:30 PM
Abstract Number: 2132

Title: Targeting PKMYT1 kinase is an effective treatment strategy in triple negative breast cancers with low molecular weight cyclin E (LMW-E) expression
Session: Biomarkers of Therapeutic Benefit 1, Sunday April 16, 2023, 1:30 PM – 5:00 PM
Abstract Number: 950

Title: Investigating Wee1 and Myt1 combined inhibition as a potential cancer therapeutic strategy
Session: Combination Therapies for Cancer, Tuesday April 18, 2023, 1:30 PM – 5:00 PM
Abstract Number: 5511