Bicycle Therapeutics Announces Presentations at the AACR Annual Meeting 2021

On April 10, 2021 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that for the first time, preclinical work describing the discovery of BT7480, a novel Nectin-4/CD137 tumor-targeted immune cell agonist (TICATM), will be presented virtually in a "New Drugs on the Horizon" session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 10-15, 2021 (Press release, Bicycle Therapeutics, APR 10, 2021, View Source [SID1234577833]). Additional work covering TICAs and Bicycle Toxin Conjugates (BTCs), will also be covered in a late-breaking mini-symposium, as well as in five e-posters.

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"Our TICA platform has made significant progress, and we are thrilled to present information about the discovery of BT7480, as well as preclinical data across multiple programs in our immuno-oncology pipeline," said Nicholas Keen, Ph.D., Chief Scientific Officer of Bicycle Therapeutics. "These presentations highlight the potential utility of Bicycle-based therapeutic candidates for treating multiple tumor types via diverse mechanisms as we pursue our goal of improving the treatment paradigm for patients with cancer."

Bicycle TICAs are potent, fully synthetic compounds that represent an immuno-oncology approach engineered to overcome the limitations of other immunomodulatory mechanisms. Bicycles are small, structurally constrained peptides discovered via phage display and optimized using structure-driven design and medicinal chemistry approaches. Bicycle has applied this disruptive technology by identifying CD137 Bicycles and chemically linking these to tumor antigen binding Bicycles to generate multifunctional molecules that induce tumor antigen-dependent, tumor-localized agonism of CD137. Bicycle expects BT7480 to enter the clinic in the second half of 2021.

Details on Bicycle’s presentations and posters at AACR (Free AACR Whitepaper) are as follows:

Poster Title: Molecular-based enrichment strategy for Nectin-4 targeted Bicycle toxin conjugate BT8009
Abstract #: 391
Session, Date and Time: Biomarkers Predictive of Therapeutic Benefit, April 10, 8:30 AM

Poster Title: Nectin-4-dependent immune cell stimulation and anti-tumor efficacy by BT7480, a Nectin-4/CD137 Bicycle tumor-targeted immune cell agonist (TICA)
Poster #: 1728
Session, Date and Time: Immunomodulatory Agents and Interventions, April 10, 8:30 AM

Poster Title: Microinjection of Nectin-4/CD137 tumor-targeted immune cell agonist (TICA) activates the local tumor microenvironment
Poster #: 1724
Session, Date and Time: Immunomodulatory Agents and Interventions, April 10, 8:30 AM

Poster Title: A multi tumor survey of Nectin-4 expression to guide BT8009 indication selection
Poster #: 1197
Session, Date and Time: Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes, April 10, 8:30 AM

Poster Title: Rapid Accumulation of Cytotoxic Payload in Tumor Tissue Drives BT5528 Activity in Tumor Models
Poster #: 1319
Session, Date and Time: Novel Drug Delivery Systems, April 10, 8:30 AM

Presentation Title: BT7480, a novel Nectin-4 dependent agonist of the immune cell costimulatory receptor CD137
Session, Date and Time: New Drugs on the Horizon: Part 1, April 10, 1:30 – 3:15 OM, Channel 1

Presentation Title: Integrative surfaceome profiling identifies immunotherapeutic targets in osteosarcoma and preclinical testing of BT1769, an MT1-MMP-targeted Bicycle toxin conjugate, in osteosarcoma by the Pediatric Preclinical Testing Consortium (PPTC)
Session, Date and Time: Late-Breaking Mini-symposium 2, April 12, 1:35 – 1:45 OM, Channel 7

The posters will be available on the Publications section of bicycletherapeutics.com following each session.

MacroGenics Announces Presentations at the 2021 AACR Annual Meeting

On April 10, 2021 MacroGenics, Inc. (Nasdaq: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 10-15, 2021 (Press release, MacroGenics, APR 10, 2021, View Source [SID1234577831]).

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"This year’s AACR (Free AACR Whitepaper) presentations highlight three antibody-based technologies upon which multiple molecules are being developed at MacroGenics," said Ezio Bonvini, M.D., Senior Vice President and Chief Scientific Officer of MacroGenics. "We are presenting pre-clinical data on MGC018, our clinical-stage, investigational antibody-drug conjugate (ADC) targeting B7-H3. At clinically relevant dose levels, MGC018 demonstrated potent antitumor activity in vivo in mouse patient-derived xenograft (PDX) models of squamous cell carcinoma of the head and neck (SCCHN). MGC018 is currently being investigated in a Phase 1 dose expansion study in advanced solid tumor cancers, including metastatic castration-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC)."

"A second poster demonstrates that margetuximab, our Fc-engineered anti-HER2 mAb developed using our Fc Optimization platform, can upregulate checkpoint molecules on Natural Killer (NK) cells, CD8 T cells and tumor cells, potentially sensitizing them to immune checkpoint blockade. Consistent with this observation, PD-1 and LAG-3 blockade by tebotelimab, our investigational bispecific PD-1 × LAG-3 DART molecule, enhances margetuximab-mediated NK cell cytolytic activity in vitro," added Dr. Bonvini. "Finally, our third poster highlights pre-clinical data on IMGC936, an investigational ADAM9-directed ADC being developed in collaboration with ImmunoGen Inc. ADAM9 is highly expressed in a large number of solid tumors and our presentation shows that IMGC936 has activity against multiple solid tumor types in in vivo mouse PDX models. IMGC936 is currently being studied in a Phase 1 clinical trial evaluating safety and pharmacokinetics in cancer patients. Together, these results illustrate the drug development potential of all three technologies MacroGenics is deploying to identify and advance promising anti-cancer drug candidates."

Presentation details are as follows:

April 10, 2021, 8:30 AM – 11:59 PM
1555 – Enhanced HER2-dependent immune activation by margetuximab, an investigational Fc-engineered anti-HER2 mAb, supports combination with checkpoint blockade
Session PO.IM02.02 – Combination Immunotherapies

April 10, 2021, 8:30 AM – 11:59 PM
950 – Targeting B7-H3 in squamous cell carcinoma of the head and neck: Preclinical proof-of-concept with the investigational anti-B7-H3 antibody-drug conjugate, MGC018
Session PO.ET07.01 – Biological Therapeutic Agents

April 10, 2021, 8:30 AM – 11:59 PM
1841 – IMGC936, an investigational ADAM9-targeting antibody drug conjugate, is active against patient-derived ADAM9-expressing xenograft models
Session PO.IM02.10 – Therapeutic Antibodies, Including Engineered Antibodies

Posters of the above presentations may be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source

MEI Pharma Reports Preclinical Data Demonstrating Ability of Voruciclib to Regulate MYC and Synergize with KRAS Inhibitors in KRAS Mutant Cancers

On April 10, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported preclinical data demonstrating that voruciclib, an orally administered cyclin-dependent kinase (CDK) inhibitor that is potent against CDK9, has single agent activity against multiple KRAS mutant cancer cell lines and synergistically inhibits growth of KRAS mutant cancers in combination with KRAS inhibitors (Press release, MEI Pharma, APR 10, 2021, View Source [SID1234577830]). The research is featured as an E-Poster Session presentation titled, "Voruciclib, a CDK9 inhibitor, downregulates MYC and inhibits proliferation of KRAS mutant cancers in preclinical models" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021. Voruciclib is currently in a Phase 1b clinical trial as a monotherapy in patients with relapsed and/or refractory B-cell malignancies and acute myeloid leukemia (AML).

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To view the poster and a multimedia announcement with additional media and investor resources click here.

"Collectively, the data reported today offer the opportunity to expand our current development activities with voruciclib and support its potential as a therapeutic option for KRAS mutated cancers in combination with direct inhibitors of KRAS," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "Beyond these data, we have ongoing efforts to explore other potential synergistic combinations in various KRAS mutated cancers as we evaluate opportunities to confirm these findings in a clinical setting."

KRAS mutated cancers are frequently associated with overexpression of MYC, a transcription factor regulating cell proliferation and growth. CDK9 is a known regulator of MYC transcription and a modulator of MYC protein phosphorylation. The data reported today in preclinical models demonstrates that voruciclib:

Results in a rapid decrease in the phosphorylation of proteins that promote MYC transcription
Rapidly decreases phosphorylation of MYC protein on Ser62, a site implicated in stabilizing MYC in KRAS mutant cancers
Possesses single agent activity against multiple KRAS mutant cancer cell lines both in vitro and in vivo
Synergistically inhibits KRAS G12C mutant cancer cell lines in combination with KRAS G12C inhibitors, both in vitro and in vivo
The full video presentation is available on our website here: View Source

About Voruciclib
Voruciclib is an orally administered CDK inhibitor differentiated by its potent in vitro inhibition of CDK9 in addition to CDK6, 4 and 1. CDK9 has important functions in cell cycle regulation, including the modulation of two therapeutic targets in cancer:

CDK9 is a transcriptional regulator of the myeloid leukemia cell differentiation protein ("MCL1"), a member of the family of anti-apoptotic proteins which, when elevated, may prevent the cell from undergoing cell death. Inhibition of CDK9 blocks the production of MCL1, which is an established resistance mechanism to the B-cell lymphoma ("BCL2") inhibitor venetoclax (marketed as Venclexta).
CDK9 is a transcriptional regulator of the MYC proto-oncogene protein ("MYC") which regulates cell proliferation and growth. Upregulation of MYC is implicated in many human cancers and is frequently associated with poor prognosis and unfavorable patient survival. CDK9, in addition to being a transcription factor for MYC, also decreases phosphorylation of MYC protein that is implicated in stabilizing MYC in KRAS mutant cancers. Targeting MYC directly has historically been difficult, but CDK9 is a promising approach to target this oncogene.
Voruciclib is currently being evaluated in a Phase 1b trial evaluating dose and schedule in patients with acute myeloid leukemia ("AML") and B-cell malignancies. Applications in solid tumors are also being explored, particularly in KRAS mutated cancers.

Investor and Analyst Video Webcast
MEI will host an investor and analyst video webcast event on Tuesday, April 13, 2021 at 8:00 AM Eastern Time reviewing data from the E-Poster Session presentation at AACR (Free AACR Whitepaper), in which MEI reported data demonstrating voruciclib downregulates MYC and synergizes with KRAS inhibitors to inhibit KRAS mutant cancers in preclinical models. The event will also include additional voruciclib data as well as an overview and update of MEI’s business.

You can access the live video webcast under the investor relations section of MEI’s website on the "Events and Presentation" page at: www.meipharma.com. A replay of the video webcast will be archived for at least 30 days after the conclusion of the live event.

Sysmex Inostics Presents SafeSEQ NGS Data at AACR for NSCLC Patients

On April 10, 2021 Sysmex Inostics, Inc., a global leader of the liquid biopsy revolution for oncology, reported the poster "Clinical evaluation of NGS-based liquid biopsy testing in non-small cell lung cancer (NSCLC) patients" at the 112th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) on April 10, 2021, from 8:30 AM – 11:59 PM Eastern Daylight Time (EDT) (Press release, Sysmex Inostics, APR 10, 2021, View Source [SID1234577829]).

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In a recent collaborative study, Johns Hopkins University School of Medicine and Sysmex Inostics’ researchers showed that the next-generation sequencing (NGS)-based liquid biopsy SafeSEQ NSCLC panel delivers equivalent performance with broader genomic coverage than testing with OncoBEAM digital PCR (dPCR). OncoBEAM technology is widely considered a gold standard for high sensitivity molecular testing and continues to be one of the most sensitive dPCR approaches.

SafeSEQ technology demonstrates ultra-sensitive detection of low-frequency mutations, with a calling threshold of 5 mutant molecules (0.025% mutant allele frequency [MAF]) from whole blood. Concordance analysis of SafeSEQ and OncoBEAM results demonstrated an overall percent agreement of 99.6% for detection of mutations in EGFR, KRAS, and BRAF (>0.1% MAF).

The 5-year survival rate for metastatic NSCLC (mNSCLC) patients is relatively low; however, it has improved with the advent of targeted therapies and uptake of circulating tumor DNA (ctDNA) based technologies in recent years. In groundbreaking NSCLC clinical trials AURA and TIGER-X, patients positive for EGFR T790M detected in plasma by OncoBEAM had equivalent outcomes to patients positive by a tissue-based assay when treated with third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), which have demonstrated potent activity against first-line EGFR TKI resistance mediated by EGFR T790M.

SafeSEQ NSCLC testing delivers broader genomic coverage than OncoBEAM, with the same ultra-sensitive detection for rare mutant molecules. Therefore, SafeSEQ is better suited to identify molecular mediators of treatment resistance to improve therapeutic strategies, delivering high-resolution monitoring of therapeutic efficacy, and enabling minimum residual disease (MRD) detection and recurrence surveillance for NSCLC patients.

Poster number LB053, "Clinical evaluation of NGS-based liquid biopsy genotyping in non-small cell lung cancer (NSCLC) patients," presented by Hillary Sloane, Associate Director of Medical & Scientific Affairs at Sysmex Inostics, will be available Saturday, April 10, 2021, from 8:30 AM – 11:59 PM EDT during the 112th Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) during Session PO.CL11.04 – Liquid Biopsies: Circulating DNA.

Phio Pharmaceuticals Presents Positive In Vivo Data Showing Strong Tumor Control for the Intratumoral Delivery of INTASYL™ RNAi Targeting PD-1

On April 10, 2021 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported new in vivo data showing intratumoral (IT) treatment with the murine PD-1 targeting INTASYL (mPH-762) inhibits tumor growth in a dose dependent fashion in PD-1 responsive and refractory models (Press release, Phio Pharmaceuticals, APR 10, 2021, View Source [SID1234577828]). Furthermore, on target efficacy was supported by modulation of immune cell populations toward antitumor phenotypes. The Company believes these data further support the potential for INTASYL mPH-762 to provide strong local immune checkpoint blockade (ICB), without the dose immune-related adverse effects (irAEs) seen with systemic ICB antibody therapy. Phio is planning to advance this program with a first-in-human clinical study of PH-762 as a directly administered drug in patients with advanced melanoma at the Gustave Roussy Institute, which is scheduled to be initiated in the fourth quarter of 2021.

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"We are pleased to announce new in vivo data today that show INTASYL mPH-762 offered strong tumor control in Hepa 1-6 and CT26 models, which are PD-1 responsive and PD-1 refractory models, respectively. The modulation of key immune cell populations in the tumor microenvironment (TME) by local application of INTASYL mPH-762 provides further evidence that the desired efficacy to treat these cancers can be attained by direct intratumoral administration. Such local administration can have several advantages such as avoiding dose limiting systemic side effects which are often dose-limiting," stated Dr. Simon Fricker, Phio’s VP of Research. "These data further support our excitement around this asset and to bring PH-762 to patients, starting with our first clinical study later this year."

All INTASYL treatments were well tolerated. Treatment with mPH-762 inhibited tumor growth in both CT26 and Hepa 1-6 models in a dose dependent manner compared to control treated tumors, with mPH-762 providing tumor growth inhibition analogous to systemic anti-PD-1 monoclonal antibody (mAb) use. Hepa 1-6 is a PD-1 inhibition-responsive hepatoma model and CT26 is a PD-1 inhibition-refractory colon cancer model. Dose-correlating on-target silencing of PD-1 protein expression across key TME cell populations was observed under treatment with mPH-762, but not with anti-PD-1 mAb. The modulation of tumor immune cell populations toward antitumor phenotypes, supporting on target efficacy, included significantly increasing overall %CD45+ and %NK1.1+ / CD45+ populations and increasing median M1 (immunostimulatory) / M2 (immunosuppressive) polarized tumor associated macrophage ratios.

These data were presented today during the AACR (Free AACR Whitepaper) Annual Meeting 2021 in a poster titled "Intratumoral INTASYL self-delivering RNAi targeting PD-1 provides in vivo tumor control and mechanistic modulation of tumor microenvironment analogous to that of systemic anti-PD-1 antibody". An archived version of the poster presentation will be made available on the "Investors – Events and Presentations" section of the Company’s website (click here).