On April 17, 2018 Advaxis, Inc. (NASDAQ: ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, reported the presentation of ADXS-HOT preclinical data in a poster discussion entitled "Targeting Shared Hotspot Cancer Mutations with a Listeria monocytogenes Immunotherapy Induce Potent Anti-Tumor Immunity" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting underway in Chicago (Press release, Advaxis, APR 17, 2018, View Source [SID1234525430]). The discussion, held yesterday, was led by Daniel O. Villarreal, Ph.D., Principal Scientist at Advaxis. The ADXS-HOT franchise leverages the Company’s proprietary Lm Technology to target common mutations in tumor driver genes.

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This study’s objective was to identify and target common (public or shared) mutations (hotspots) and to determine if the ADXS-HOT platform could effectively target those hotspots and control tumor growth. Results indicate that ADXS-HOT could achieve this in preclinical models against single and multi-target constructs. The full abstract is available here: View Source
"The results of this preclinical work with ADXS-HOT represent an exciting opportunity that may allow us to develop disease-specific immunotherapies that have the potential to be effective against multiple targets, capable of generating high-avidity T cells against shared of public mutations, as well as multiple proprietary highly immunogenic cancer-testes and oncofetal antigens for multiple tumor types," said Robert G. Petit, Ph.D., Executive Vice President and Chief Scientific Officer of Advaxis. "Additionally, the results show increased functionality and resiliency in CD8 T cells upon restimulation, indicating the potential not only to increase the number and frequency of CD8 T cells, but to strengthen them."

About ADXS-HOT
ADXS-HOT leverages the Company’s proprietary Lm technology to target common "hotspot" mutations. ADXS-HOT products are designed to target acquired shared or "public" mutations in tumor driver genes along with cancer-testes and oncofetal tumor-associated antigens that are shared by multiple patients. Although ADXS-HOT has not been tested in patients, in theory, products would be designed to treat all patients with a particular type of cancer, without the need for pre-treatment testing, biopsy, DNA sequencing or diagnostic testing.

On April 17, 2018 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for cancer and autoimmune/inflammatory diseases, reported preclinical study results of its ALPN-202 immuno-oncology program (Press release, Alpine Immune Sciences, 17 17, 2018, View Source [SID1234525447]). ALPN-202 will be the second product candidate to come out of the company’s proprietary scientific platform following ALPN-101, which is projected for an IND filing in the fourth quarter of 2018.

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ALPN-202 is designed to antagonize PD-L1 and CTLA-4 while also providing CD28 costimulation. Recent literature suggests the lack of CD28 costimulatory signaling may be a principal reason why many tumors do not respond to PD-L1 or CTLA-4 blockade. ALPN-202’s ability to agonize the costimulatory receptor CD28 potentially improves the immune system’s response to cancer.

Alpine used its proprietary scientific platform to engineer Variant Ig Domains (vIgDs) based on CD80. Single vIgD proteins were created capable of binding PD-L1, CTLA-4, and CD28. These vIgDs were then fused to an Fc backbone and used in various in vitro and in vivo studies to characterize functional activity and assess anti-tumor activity in mice implanted with human PD-L1 transduced tumors. Results showed:

ALPN-202 eliminated tumors in most mice (73% or 8/11 tumor free) compared to durvalumab, an FDA-approved anti PD-L1 antibody (18% or 2/11 tumor free), and controls (0/11 tumor free).
Importantly, those mice tumor free after receiving ALPN-202 were re-challenged with tumor and 100% of them were resistant to the newly-implanted cells without receiving additional doses of therapy, suggesting the potential for ALPN-202 to induce anti-tumor memory.
ALPN-202 elicited CD28 costimulation only in the presence of PD-L1.
Scientific Support and Rationale for ALPN-202
PD-1/PD-L1 inhibitors likely are most effective only when sufficient T cell activating signals, such as via CD28 costimulation, are present. Indeed, recent research demonstrated CD28 costimulation appears to be required for PD-1 inhibition to rescue exhausted T cells in some settings (Science 355:1423, 2017), yet the CD28 ligands CD80 and/or CD86 are often poorly expressed in tumor microenvironments. Because it provides both checkpoint blockade and CD28 costimulation, the ALPN-202 program is therefore well positioned to potentially be a more potent and broadly applicable therapeutic.

"Previously published data suggest PD-1 blockade requires CD28 costimulation to work, at least in some cancers. The preclinical data we are presenting at AACR (Free AACR Whitepaper) indicate the ALPN-202 program proteins are capable of delivering both with a single molecule," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "Additionally, these data demonstrate we can modulate three targets (PD-L1, CTLA-4, and CD28) with a single domain (in contrast to the need for multiple targeting domains for other therapeutic formats like bi- or tri-specific antibodies), demonstrating the potential promise of our versatile scientific platform."

"Our goal in oncology is to develop paradigm-shifting therapeutics that meaningfully improve upon existing therapies like PD-1/PD-L1 inhibitors," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine. "The preclinical data presented at AACR (Free AACR Whitepaper) show ALPN-202 antagonizes PD-1 and CTLA-4, and provides a CD28 costimulatory signal, resulting in a potent anti-tumor response. As we drive the ALPN-202 program towards the clinic in 2019, we believe we can create the next generation of immuno-oncology therapeutics with novel mechanisms of action using our proprietary scientific platform."

On April 17, 2018 Apexian Pharmaceuticals, a clinical-stage biotechnology company focused on developing safe and effective therapy for patients with high unmet medical needs, reported that it will present two key poster sessions at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Meeting, which will be held at McCormick Place in Chicago, Illinois from April 14 – 18, 2018 (Press release, Apexian Pharmaceuticals, APR 17, 2018, View Source [SID1234525431]). Dr. Mark Kelley, Apexian’s Chief Scientific Officer, along with the research team will available at the posters session. The company will present two posters on combination therapy of APX3330 in pancreatic cancer and APE1 signaling pathway.

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The titles and locations for these sessions are:
"Combination Therapy in PDAC Involving Blockade of the APE1/Ref-1 Signaling Pathway: An Investigation into Drug Synthetic Lethality and Anti-Neuropathy Therapeutic Approach"
Session Date and Time: Tuesday, April 17, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 37
"APE1/Ref-1 Redox Signaling Regulates HIF1a-mediated CA9 Expression in Hypoxic Pancreatic Cancer Cells: Combination Treatment in Patient-derived Pancreatic Tumor Models"
Session Date and Time: Monday, April 16, 2018 from 1:00 – 5:00 PM
Location: McCormick Place South, Exhibit Hall A, Poster Section 41
The poster sessions will add significant new information gathered on the effectiveness of Apexian’s lead clinical candidate, APX3330, and the ongoing research on the APE1/Ref-1 target.

On April 16, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported the presentation of updated data from its ongoing Phase 1 clinical trial of DCC-2618, the Company’s broad spectrum KIT and PDGFRα inhibitor, in patients with gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, APR 16, 2018, View Source [SID1234525340]). Filip Janku, M.D., Ph.D., Assistant Professor, The University of Texas MD Anderson Cancer Center presented the poster titled "Pharmacokinetic (PK), safety, and tolerability profile of DCC-2618 in a phase 1 trial supports 150 mg QD (once daily) selected for a pivotal phase 3 trial in gastrointestinal stromal tumors (GIST)" at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Chicago, IL. The poster includes an assessment of the safety and tolerability profile of DCC-2618 in 100 GIST patients treated at the recommended Phase 2 dose (RP2D) of 150 mg QD, which supports the selection of this dose for the ongoing pivotal, randomized Phase 3 INVICTUS study (NCT03353753).

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"The data presented at AACR (Free AACR Whitepaper) provides a robust assessment of the safety and tolerability profile of DCC-2618 in GIST patients at the 150 mg QD dose selected for the INVICTUS pivotal Phase 3 study in fourth-line and fourth line plus GIST, which we initiated in January 2018," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "If successful, the INVICTUS study could serve as the basis for a New Drug Application (NDA), providing a much-needed therapeutic option for these patients for whom there are no approved treatment options. We also plan to initiate a second Phase 3 registration study later this year, evaluating DCC-2618 in second-line GIST patients who have progressed, or are intolerant to front-line therapy with imatinib."

The poster presentation includes the following highlights:
Safety and tolerability of DCC-2618 on 100 GIST patients treated at the 150 mg QD dose out of the total of 169 patients treated with DCC-2618, as of the cut-off date of January 18, 2018.
As of March 19, 2018, 81 of 137 GIST patients enrolled at the cut-off date and treated at 100 mg or more per day, remained on study treatment. In addition, 46 patients were treated for more than 6 months, including 10 patients who were treated for more than 12 months.
Employing a population pharmacokinetic (PK) model based on steady state exposure to DCC-2618 and the active metabolite, DP-5439, increasing doses of DCC-2618 resulted in dose proportional increases in the combined exposure.

Preliminary data from the 12 GIST patients dose escalated from 150 mg QD to 150 mg BID following progression by RECIST (Response Evaluation Criteria in Solid Tumors) are immature and do not currently support a conclusion regarding a benefit from intra-patient dose escalation.
Based on the 100 GIST patients treated at the RP2D dose of 150 mg QD, DCC-2618 was well-tolerated, supporting the use of this dose in the pivotal, randomized Phase 3 trial, INVICTUS (NCT03353753).

About DCC-2618
DCC-2618 is a KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, systemic mastocytosis and glioblastoma multiforme. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting a broad spectrum of mutations in KIT and PDGFRα. DCC-2618 is a KIT and PDGFRα inhibitor that blocks initiating KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST as well as the primary D816V exon 17 mutation involved in SM. DCC-2618 also inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

On April 16, 2018 Personalis, Inc., a provider of advanced genomic sequencing and analytics for immuno-oncology, reported that the company will present four posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held this year in Chicago, Illinois from April 14-18, 2018 (Press release, Personalis, APR 16, 2018, View Source [SID1234525356]).

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Following is a list of abstracts that will be presented at the meeting.

Session ID / Poster Number

Title & Presenter
Day & Time
Location
PO.BSB01.01
1292
Methods of improving accuracy of neoantigen identification for therapeutic and diagnostic use in immuno-oncology
Presenter: Sean Michael Boyle
April 16
8am-12pm
Poster section
12
PO.BSB01.02
2245
Deconvolution of diverse immune cell populations within tumors using ACE Transcriptome
Presenter: Eric Levy
April 16
1-5pm
Poster section
12
PO.MCB09.08
5385
Supporting neoantigen discovery and monitoring in plasma through analytical validation of a deep Augmented Content Enhanced (ACE) exome
Presenter: Ravi Alla
April 18
8am-12pm
Poster section
17
PO.IM02.04
5710
Molecular profiling of anti-PD-1 treated melanoma patients reveals importance of assessing neoantigen burden and tumor escape mechanisms for clinical treatment
Presenter: Sean Michael Boyle