On June 22, 2020 HiFiBiO Therapeutics is presenting its three lead pipeline programs at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II taking place today (Press release, HiFiBiO Therapeutics, JUN 22, 2020, View Source [SID1234561300]). The company is a pioneer of novel antibody drug discovery and development leveraging single-cell analytics to treat cancer, autoimmune and infectious diseases. HiFiBiO invites members of the scientific and medical communities to listen to these poster presentations online at the AACR (Free AACR Whitepaper) meeting website or, after the AACR (Free AACR Whitepaper) meeting has concluded, at the HiFiBiO Therapeutics website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These presentations demonstrate the rapid progress spearheaded by our scientists at HiFiBiO and the development of our pipeline, and we look forward to soon moving our lead programs to IND," said Liang Schweizer, PhD, President and CEO of HiFiBiO Therapeutics. "Given our depth of experience in immune modulation and cutting-edge single-cell science and technology, we believe that HiFiBiO is realizing the potential of single-cell analysis to develop novel, high-quality antibody targets into life-changing treatment options for patients."

POSTER PRESENTATION DETAILS:

Title: HFB301001, a novel OX40 agonistic antibody with a unique pharmacological profile and innovative biomarker strategy
Presenters: Andreas Raue, PhD, Project Leader, Senior Director, Head of Drug Intelligent Science (DIS) at HiFiBiO Therapeutics and Robert Petit, PhD, Senior Scientific Advisor
E-Poster: #2285
HFB301001 is being developed as a potential novel treatment option for cancer coupled with a patient stratification biomarker in solid tumor indications.

Title: Discovery and characterization of novel TNFR2 antibodies to modulate T cell activities in immunosuppressive environment
Presenters: Francisco Adrian, PhD, Senior Vice President, Head of Research and Shuo Wei, PhD, Project Leader, Principal Scientist, Disease Biology
E-Poster: #2282
HFB200301 is an anti-TNFR2 monoclonal antibody being developed as a potential first-in-class therapeutic for the treatment of biomarker-selected patients with advanced cancer.

Title: HFB9-2, a novel Galectin-9 neutralizing antibody to reverse immune suppression in the tumor microenvironment
Presenters: Roshan Kumar, PhD, Senior Director, Head of Discovery Biology and US External Innovation and Yun-Yueh Lu, PhD, Project Leader, Principal Scientist, Disease Biology
E-Poster: #6532
HFB2009 program focuses on developing anti-Gal-9 neutralizing antibodies as a potential first-in-class treatment for AML and solid tumors, both as a single agent and a combination therapy.

More information about these and other programs in the HiFiBiO Therapeutics pipeline is available at View Source

On June 22, 2020 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 a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting which further details data demonstrating the potential of a TIGIT targeting INTASYL compound as an immuno-oncology therapeutic through the suppression of TIGIT in the tumor microenvironment (TME) (Press release, Phio Pharmaceuticals, JUN 22, 2020, View Source [SID1234561299]). The Phio poster presentation will also be available under the "Investors – Events and Presentations" section of the Company’s website (click here).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In our poster presentation at the AACR (Free AACR Whitepaper) 2020 Virtual Annual Meeting, we announced detailed data supporting the potential for PH-804, our TIGIT targeting INTASYL compound, as an immuno-oncology therapeutic and a viable alternative to anti-TIGIT antibodies. This data provides insight around the mechanisms of action of the tumor growth suppression with PH-804, as previously announced from a study in a validated animal model, namely through increases in immune cell count and immune cell activation in the tumor micro-environment," said Dr. Simon Fricker, Phio’s VP of Research. "These preclinical results build upon the recent data we announced at the ASCO (Free ASCO Whitepaper) 2020 Annual Meeting that show the ability and safety of INTASYL RNAi technology to reprogram immune cells, such as T cells or NK cells, to improve their efficacy."

In an in vivo study, tumor growth inhibition was determined for both PH-804 and an anti-TIGIT antibody in colorectal carcinoma tumor bearing mice. Results from the study demonstrated that our INTASYL compound was efficiently delivered intratumorally to immune cells, resulting in a dose dependent inhibition of tumor growth, reaching statistical significance levels for PH-804 and anti-TIGIT antibody treatment arms. More detailed data from the study provides evidence of an "on-target" effect of PH-804 as shown by silencing of TIGIT mRNA expression in tumor infiltrating lymphocytes isolated from the treated tumors. In addition, analysis of the TME of the PH-804 treated mice showed a dose dependent increase in cytotoxic effector T cells, and a dose dependent activation of such T cells as shown by the expression of activation makers such as CD25 and CD69.

These data demonstrate the potential of a TIGIT targeting INTASYL compound for the suppression of TIGIT in the TME and support the hypothesis that local TIGIT silencing with INTASYL is a promising therapeutic approach.

On June 22, 2020 Alkermes plc (Nasdaq: ALKS) and Clovis Oncology, Inc. (Nasdaq: CLVS) reported positive preclinical data from a study designed to evaluate the combination potential of ALKS 4230, Alkermes’ investigational engineered interleukin-2 (IL-2) variant immunotherapy, with lucitanib, Clovis’ investigational angiogenesis inhibitor (Press release, Clovis Oncology, JUN 22, 2020, View Source [SID1234561298]). The data will be presented during a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, taking place June 22-24, 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study evaluated the antitumor efficacy and mechanism of action of mALKS 4230, a mouse ortholog of ALKS 4230, and lucitanib as monotherapies and in combination in a preclinical syngeneic mouse model of colon cancer. The combination of mALKS 4230 with lucitanib resulted in dose-dependent, durable complete responses (absence of any detectable tumor) and enhanced survival compared with monotherapy treatment with mALKS 4230 and lucitanib.

"Combining treatments with complementary mechanisms may offer synergistic clinical benefit and expand treatment options for a broader set of patient populations," said Craig Hopkinson, M.D., Chief Medical Officer and Executive Vice President of Research & Development at Alkermes. "These compelling preclinical data provide a foundational rationale to further explore novel combination options, such as an angiogenesis inhibitor, for ALKS 4230, with the goal of bringing improved therapeutic outcomes to patients across multiple tumor types."

Key findings presented in the poster include the following:

In the group that received the higher dose of mALKS 4230 (out of two doses tested) combined with lucitanib, 100 percent of the treated mice exhibited complete tumor regression and protection from new tumor growth upon re-challenge, an indication of the development of immunological memory.
The combination of mALKS 4230 with lucitanib resulted in an increase in intratumoral immune cells, including CD8+ T cells and dendritic cells, compared to monotherapy treatment, changes that are associated with anti-tumor immune responses.
The combination of mALKS 4230 with lucitanib elicited a distinct gene expression profile associated with anti-tumor activity, including increased immune cytolytic gene expression with decreased expression of genes with pro-angiogenic functions.
A virtual poster titled, "The Combination of a Mouse Ortholog of ALKS 4230, a Selective Agonist of the Intermediate-Affinity IL-2 Receptor, and the Angiogenesis Inhibitor Lucitanib Enhances Antitumor Activity," along with a pre-recorded audio presentation by Dr. Jared Lopes, Principal Scientist, Alkermes will be available on the AACR (Free AACR Whitepaper) website at View Source

About ALKS 4230

ALKS 4230 is an investigational, novel, engineered fusion protein comprised of modified interleukin-2 (IL-2) and the high affinity IL-2 alpha receptor chain, designed to selectively expand tumor-killing immune cells while avoiding the activation of immunosuppressive cells by preferentially binding to the intermediate-affinity IL-2 receptor complex. The selectivity of ALKS 4230 is designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.

About Lucitanib

Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3). Emerging clinical data support the combination of angiogenesis inhibitors and immunotherapy to increase effectiveness in multiple cancer indications. Angiogenic factors, such as vascular endothelial growth factor (VEGF), are frequently up-regulated in tumors and create an immunosuppressive tumor microenvironment. Use of antiangiogenic drugs reverses this immunosuppression and can augment response to immunotherapy.

Lucitanib is an unlicensed medical product.

On June 22, 2020 Ascendis Pharma A/S (Nasdaq: ASND), a biopharmaceutical company that utilizes its innovative TransCon technologies to address unmet medical needs, reported the presentation of preclinical data for TransCon IL-2 β/γ, an oncology product candidate designed to provide sustained systemic release of a receptor-biased IL-2 (IL-2 β/γ), at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II from June 22 to June 24, 2020 (Press release, Ascendis Pharma, JUN 22, 2020, View Source [SID1234561294]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Our preclinical results have demonstrated that TransCon IL-2 β/γ selectively binds and activates the IL-2 β/γ receptor and provides sustained and long-lasting exposure. By applying our TransCon technology to this clinically validated cytokine, we have overcome the two most significant limitations of IL-2 therapy, improving both the receptor-binding properties and the pharmacokinetic profile," said Juha Punnonen, M.D., Ph.D., Ascendis Pharma’s Senior Vice President and Head of Oncology. "Based on the promising preclinical results we’ve seen with our TransCon IL-2 β/γ and TransCon TLR7/8 Agonist product candidates, we believe our TransCon technologies – which enable systemic and long-acting intratumoral administration – have the potential to improve treatment outcomes in cancer patients. We look forward to our first Investigational New Drug application, or similar, in oncology later this year for TransCon TLR7/8 Agonist, followed by a planned filing for TransCon IL-2 β/γ in 2021."

TransCon IL-2 β/γ is a novel long-acting prodrug of IL-2 β/γ designed to address limitations of alternative IL-2 treatments, including aldesleukin, which has been available since the 1990’s as a treatment for advanced kidney cancer and advanced melanoma. TransCon IL-2 β/γ is designed with a parent drug that selectively binds and activates the IL-2Rβ/γ. By applying the innovative TransCon technology platform, preclinical data also showed that TransCon IL-2 β/γ demonstrated a long in vivo half-life of approximately 32 hours, expected to support potential dosing of every three weeks in patients. Preclinical results show a single dose of TransCon IL-2 β/γ selectively expanded lymphocyte counts (CD8+ T cells and NK cells) in non-human primates, with minimal signs of systemic inflammation (IL-5 and IL-6 markers) or endothelial cell damage (E-Selectin and VCAM-1 markers) and no dose-limiting toxicities.

Presentation Details

American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II

Title Date/Time
P4507: TransCon IL-2 β/γ: a novel long-acting prodrug of receptor-biased IL-2 designed for improved pharmocokinetics and optimal activation of T cells for the treatment of cancer Monday, June 22, 2020

8:45 a.m. Eastern

The poster is available on the company’s website under Selected Publications in the Pipeline section:

View Source

About TransCon Oncology Programs

Ascendis Pharma is developing potentially best-in-class oncology therapies by applying its TransCon technologies for systemic and intratumoral administration to clinically validated pathways in order to improve efficacy and reduce systemic toxicity. Multiple oncology programs are currently in preclinical evaluation.

About TransCon Technology

TransCon refers to "transient conjugation." The proprietary TransCon platform is an innovative technology to create new therapies that are designed to potentially optimize therapeutic effect, including efficacy, safety and dosing frequency. TransCon molecules have three components: an unmodified parent drug, an inert carrier that protects it, and a linker that temporarily binds the two. When bound, the carrier inactivates and shields the parent drug from clearance. When injected into the body, physiologic conditions (e.g., pH and temperature) initiate the release of the active, unmodified parent drug in a predictable manner. Because the parent drug is unmodified, its original mode of action is expected to be maintained. TransCon technology can be applied broadly to a protein, peptide or small molecule in multiple therapeutic areas, and can be used systemically or locally.

On June 22, 2020 AIMM, a privately-held biopharmaceutical company, reported it has presented preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting from its antibody programs in oncology using a rich pipeline of tumor- specific antibodies from cured cancer patients (Press release, AIMM Therapeutics, JUN 22, 2020, View Source [SID1234561293]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Recognizing that cured cancer patients have benefited, directly or indirectly, from a robust and specific antibody response, AIMM has set out to select those functional antibodies as a starting point for its drug development programs," said John Womelsdorf, Ph.D., chief executive officer of AIMM Therapeutics. "AIMM is perfectly positioned to advance this approach; firstly, through our ability to interrogate the entire B cell repertoire of the surviving patient and identify novel targets and anti-cancer antibodies using our AIMSelect platform. And, secondly, we are able to potentiate these antibodies for use as therapies through our AIMProve platform to leverage the unique biology that was underlying the original donor’s successful clinical response."

AIMM has a pipeline of multiple drug candidates that bind to novel cancer targets and epitopes. The company’s lead asset, AT1412, is a CD9-targeted antibody derived from a stage 4 melanoma patient with brain metastasis who was successfully treated with autologous T-cell based immunotherapy and is still tumor-free after 13 years despite having an aggressive cancer. AT1412 is going through the last stages of preclinical development for B-cell lymphoblastic leukemia/lymphoma (B-ALL) and CD9+ solid tumors, such as melanoma, gastric, breast, and esophageal cancers. Preclinical data from studies of AT1412 in B-ALL and melanoma tumor models show monotherapy treatment induced full tumor rejection that in the case of melanoma can be further sustained in combination with nivolumab. Two posters presented at AACR (Free AACR Whitepaper) demonstrate the potential for AT1412 to be a potent antibody capable of inducing cell death and facilitating the trafficking of immune cells into the tumor microenvironment.

Additionally, several antibody candidates, such as CD3-bispecific/ADC/CAR-T assets, are in lead optimization and could provide for multiple non-dilutive partnering opportunities and co-development collaborations. AT1413, isolated from an M5 acute myeloid leukemia patient that underwent allograft stem cell transplantation, has the potential to be formatted into a CD3-bispecific, ADC or CAR-T. Another poster presented at AACR (Free AACR Whitepaper) describes two different bispecific T-cell engaging forms of AT1413 that induce strong anti-tumor cytotoxic activities in AML and solid tumors like melanoma and breast carcinoma. A fourth poster presented at the AACR (Free AACR Whitepaper) annual meeting reviews AT1636, an antibody targeting a cancer- specific glyco-modified antigen, which was retrieved from a patient with Lynch syndrome.

Hans van Eenennaam, Ph.D., who joined AIMM Therapeutics in 2019 as its chief scientific officer and is credited as a co-inventor of pembrolizumab, added, "Using patient-derived antibodies as therapeutics represents an exciting approach to drug development because they are unlocking novel targets and mechanisms of action. As exemplified by our AT1412 (anti-CD9 antibody), we have identified that this patient-derived antibody induces antibody-mediated tumor kill and promotes immune cell penetration into the tumor. Our technologies were initially developed and validated for applications in infectious disease, resulting in the out licensing of a product candidate for respiratory syncytial virus to MedImmune that is now in Phase 3 development. Following years of groundbreaking experience in the field led by my predecessor and founder of the company Hergen Spits, professor at the Academic Medical Center in Amsterdam, we are now applying our evolved and highly selective antibody technologies to treat cancer. Our unique and proprietary technology allows us to interrogate every memory B-cell in both human blood and tumors for anti-cancer reactivity. Together with our rich tradition of cutting-edge immunology, we are uniquely positioned to identify targets on both hematological and solid tumors that have not been previously identified before."

AACR Presentations on June 22, 2020
Poster 531, Session: Antibody Technologies
AT1412, a patient-derived antibody in development for the treatment of cd9-positive precursor b-acute lymphoblastic leukemia

Poster 532, Session: Antibody Technologies
A patient-derived anti-CD9 antibody induces tumor rejection and synergistically enhances anti-PD1 activity

Poster 542, Session: Antibody Technologies
T-cell engager bispecific formats of an AML patient-derived antibody targeting a unique sialylated CD43 epitope induce kill of melanoma cells in vitro and in vivo

Poster 5163, Session: Antibody Technologies
A colon cancer survivor-derived antibody recognizes a previously unidentified truncated, O-mannosylated 70kDa variant of E-cadherin