On March 29, 2019 Forbius, a clinical-stage company that develops novel biologics for the treatment of fibrosis and cancer, reported that it will report the results from its Phase 1 dose-finding trial with novel, tumor selective, anti-epidermal growth factor receptor (EGFR) antibody-drug conjugate (ADC) AVID100 at the AACR (Free AACR Whitepaper) Annual Meeting 2019 (Press release, Forbius, MAR 29, 2019, View Source [SID1234534768]). An additional AACR (Free AACR Whitepaper) poster presentation will feature preclinical data confirming AVID100’s novel mechanism of action, which potently targets tumor cells while sparing EGFR-expressing non-tumor cells.

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Details and highlights of the presentations are as follows:

CT056 / 13 – A Phase Ia/IIa trial of AVID100, an anti-EGFR antibody-drug conjugate

Poster presentation: April 1, 8:00 AM – 12:00 PM EDT, Section 17
Author: N. Lakhani
(Abstract available here)

AVID100 was well-tolerated in a Phase 1 dose-escalation study in patients with advanced solid tumors of epithelial origin (any EGFR status)
Most common treatment-related adverse events (TRAEs, in > 25% patients) were rash (66.7%; grade 1 or 2), nausea (41.7%; grade 1 or 2), and fatigue (29.2%; grade 1 or 2)
Recommended Phase 2 dose (RP2D) of 220 mg/m2 (~6 mg/kg) confirmed, one of the highest RP2Ds reported for maytansinoid payload ADCs (Deslandes, 2014)
Phase 2 (AVID100-01; NCT03094169) enrollment ongoing to evaluate AVID100 efficacy, safety, and tolerability in patients with EGFR-overexpressing (IHC 3+) SCCHN and sqNSCLC
218 / 9 – AVID100 is an anti-EGFR ADC that promotes DM1-meditated cytotoxicity on cancer cells but not on normal cells

Poster presentation: March 31, 1:00 PM – 5:00 PM EDT, Section 9
Author: M. Thwaites
(Abstract available here)

AVID100 is highly potent and selectively cytotoxic against EGFR-expressing cancer cells, while sparing normal EGFR-positive keratinocytes
Protection of EGFR-expressing normal cells is shown to be a function of AVID100’s antibody moiety, which inhibits EGFR signaling and proliferation in normal cells
About AVID100 and the AVID100-01 Trial

AVID100 is a highly potent EGFR-targeting antibody-drug conjugate (ADC) that was engineered to achieve enhanced anti-tumor efficacy without a corresponding increase in toxicity against skin and other EGFR-expressing normal tissues. In preclinical studies, AVID100 demonstrated significant anti-cancer activity, including in EGFR-overexpressing tumor models that are resistant to marketed EGFR inhibitors. AVID100 is the only anti-EGFR ADC in clinical development that targets both wild-type and mutant forms of EGFR.

In a successfully completed Phase 1 study, AVID100 reported a recommended Phase 2 dose (RP2D) of 220 mg/m2 (~6mg/kg), which is expected to be in the therapeutically active range based on preclinical efficacy studies. Treatment was generally well-tolerated, with the majority of treatment-related adverse events in the Phase 1 trial at RP2D being grade 1 or 2 in severity.

AVID100-01 (NCT03094169) is an open label, multicenter, dose-escalation study to evaluate the safety and efficacy of AVID100 in patients with confirmed EGFR-overexpressing tumors.

On March 29, 2019 Kymera Therapeutics Inc., a biotechnology company pioneering targeted protein degradation to create breakthrough medicines for patients, reported that it will present new preclinical data for its first-in-class oral IRAK4 protein degrader, KYM-001, in MYD88-mutant lymphoma (Press release, Kymera Therapeutics, MAR 29, 2019, View Source [SID1234534793]). Data will be presented in a late-breaking research session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 3 from 8 a.m. – 12 p.m. (Poster #18, Session: Experimental and Molecular Therapeutics 2). The study showed that KYM-001 led to highly selective degradation of IRAK4 and tumor regression upon oral dosing, both alone and in combination with BTK inhibition.

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"IRAK4 degraders offer an entirely new therapeutic approach to treat MYD88-driven B cell lymphomas, which are often aggressive and have a poor prognosis," said Nello Mainolfi, PhD, co-founder and Chief Scientific Officer, Kymera Therapeutics and study co-author. "IRAK4 kinase and scaffolding functions are critical to MYD88-driven Myddosome signaling. Unlike conventional kinase inhibitors, our novel degrader KYM-001 removes both the kinase and scaffolding function of IRAK4 to effectively block Myddosome signaling, resulting in tumor growth arrest and subsequent regression. The team has been able to very quickly identify orally active degraders that offer ease and flexibility of dosing. "

MYD88-activating mutations occur in 30-40% of patients with activated B cell-like (ABC) diffuse large B cell lymphoma (DLBCL). This study assessed the antitumor activity of Kymera’s orally active small molecule degraders in human ABC DLCBL cell lines in vitro and in tumor xenograft models in vivo, alone and in combination with the BTK inhibitor ibrutinib.

Study Highlights "KYM-001, a first-in-class oral IRAK4 protein degrader, induces tumor regression in xenograft models of MYD88-mutant ABC DLBCL alone and in combination with BTK inhibition":

KYM-001 induced potent and selective E3 ligase-dependent degradation of IRAK4 in multiple cellular models, resulting in 90% degradation at concentrations less than 100 nM.
KYM-001 induced comparable levels of IRAK4 degradation in both MYD88 mutant and MYD88 WT human ABC DLBCL cell lines.
KYM-001 impacted viability in MYD88 mutant, but not WT, ABC DLBCL cell lines, inducing apoptotic effects within 72 hours.
Oral dosing of KYM-001 showed dose-dependent antitumor activity against the MYD88 L265P mutant ABC DLBCL cell line OCI-LY10, with >80% degradation of IRAK4 correlating with tumor regression in xenograft-bearing mice.
KYM-001 was synergistic with the BTK inhibitor ibrutinib in vitro in ABC DLBCL cell lines bearing both MYD88 L265P and CD79 mutations. In vivo, this combined activity resulted in tumor regression at concentrations that were sub-optimal in single-agent studies, supporting further exploration of combinations that target oncogenic NFκB signaling.

On March 29, 2019 Immunomic Therapeutics, Inc. reported its late-breaking preclinical data which shows that its investigational nucleic acid platform, UNITE, may enhance antitumor immunity when used in connection with its investigational DNA vaccine, ITI-7000 (Press release, Immunomic Therapeutics, MAR 29, 2019, View Source [SID1234534890]). In preclinical studies, ITI-7000, an investigational DNA vaccine targeting ErbB2/HER2, demonstrated robust activation of known anti-tumor CD4 and CD8 cells in vivo and promoted tumor infiltration with activated CD8 T cells. These data are presented today at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2019 meeting in Atlanta, Georgia.

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In addition to observing activation of known anti-tumor CD4 and CD8 cells in vivo, Immunomic scientists observed the overexpression of PDL1 in the tumor microenvironment. This pathway has shown clinical relevance as a cancer immunotherapy target of the tumor microenvironment. PDL1 overexpression upregulated by ITI-7000 suggests that a combination of ITI-7000 with an anti-PD1/PDL1 therapy may increase the therapeutic potential of either agent on its own. This data also supports the prevailing belief in the immunotherapy community that cancer vaccination could synergize with anti PD1 and PDL1 and other immunotherapies, as well as support the viability of the UNITE platform as a means to do so. In summary, these findings support the potential of ITI-7000 as a cancer vaccine and highlight that UNITE, Immunomic’s nucleic acid platform, may have the potential to enhance immunity of investigational cancer therapies.

View the poster.

Poster Title: DNA vaccine co-expressing Her2/ErbB2 antigen, fused with LAMP, elicits strong antitumor effects in vivo by increasing tumor infiltration with CD8+ T cells
Session Category: Immunology
Session Title: Late-Breaking Research: Immunology 2
Session Date and Time: Tuesday, April 2, 2019 8:00 AM- 12:00 PM
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 42

On March 29, 2019 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE:CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address cancer, liver and inflammatory diseases, reported that it has filed its annual report on Form 20-F for the fiscal year ended December 31, 2018 with the U.S. Securities and Exchange Commission (the "SEC") (Press release, Can-Fite BioPharma, MAR 29, 2019, View Source [SID1234534769]).

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The annual report, which contains the Company’s audited consolidated financial statements, can be accessed on the SEC’s website at View Source as well as via the Company’s investor relations website at View Source

The Company will deliver a hard copy of its annual report, including its complete audited consolidated financial statements, free of charge, to its shareholders upon request to Can-Fite Investor Relations at 10 Bareket Street, Kiryat Matalon, Petah-Tikva 4951778, Israel or by phone at +972-3-9241114.

On March 29, 2019 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer, reported that management will host a conference call and webcast on Tuesday, April 2, 2019 at 8:00 am ET / 1:00 pm BST to discuss initial data on the AUTO1 ALLCAR19 Phase 1/2 trial in adult acute lymphoblastic leukemia (ALL) being presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 1, 2019 in Atlanta, Georgia (Press release, Autolus, MAR 29, 2019, View Source [SID1234534795]).

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Claire Roddie, MB PhD FRCPath, consultant hematologist, University College London Hospital and honorary senior lecturer, University College London, will deliver the poster presentation. Details include:

Abstract Number: CT105
Session Name: PO.CT04 – Phase I-III Trials in Progress: Part 1
TITLE: AUTO 1, a novel fast off CD19CAR delivers durable remissions and prolonged CAR T cell persistence with low CRS or neurotoxicity in adult ALL
Session Date: Monday, April 1, 2019
Session Time: 1:00 PM – 5:00 PM ET
Location: Georgia World Congress Center, Exhibit Hall B, Poster Section 17

The full text of the abstract is available on the AACR (Free AACR Whitepaper) website at View Source!/6812/presentation/9977.

Conference Call Information
Autolus management will host a conference call featuring Dr. Roddie on Tuesday, April 2, 2019 at 8:00 am ET/ 1:00 pm BST to discuss the ALLCAR19 data presented at AACR (Free AACR Whitepaper). To listen to the webcast and view the accompanying slide presentation, please go to View Source

The call may also be accessed by dialing 866-679-5407 (U.S.) or 409-217-8320 (international) and referencing conference ID 7679666. After the conference call, a replay will be available for one week. To access the replay, please dial 855-859-2056 (U.S.) or 404-537-3406 (international) and enter conference ID 7679666.

About AUTO1
AUTO1 is a CD19 CAR T cell investigational therapy designed to overcome the limitations in safety – while maintaining similar levels of efficacy – compared to current CD19 CAR T cell therapies. Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T cells, AUTO1 may reduce toxicity and be less prone to T cell exhaustion, which could enhance persistence and improve the T cells’ abilities to engage in serial killing of target cancer cells. In 2018, Autolus signed a license agreement under which Autolus acquired global rights from UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase 1 trials, one in pediatric ALL and one in adult ALL.
For information about the trials, visit View Source and
View Source

About Adult Acute Lymphoblastic Leukemia
According to the American Cancer Society, acute lymphoblastic leukemia (ALL) is predicted to affect approximately 5,960 adults in the United States in 2018. Combination chemotherapy enables 90% of adult patients to experience CR (complete response). Despite this, the prognosis of adult ALL is still poor and has not changed significantly during the last two to three decades, with long-term remission rates limited to 30–40%. Approximately 50% of all adult ALL patients will relapse.