On May 15, 2020 Syntekabio (KOSDAQ: 226330), an AI and NGS based drug development company, reported the result of STB-C017 animal experiments, a small molecule IDO/TDO dual inhibitor derived by Syntekabio’s AI drug discovery solution, at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, today at 00:00 EDT (Press release, Syntekabio, MAY 15, 2020, View Source [SID1234558193]).

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The triple combination ofThe triple combination of STB-C017, aPD-1 and aCTLA-4 prolongs overall survival
Chan Kim, M.D., Ph.D., associate professor of CHA Bundang Medical Center and the presenter of the research, stated, "STB-C017 significantly enhanced immuno-oncologic effect compared to epacadostat. It also derived multiple CRs when combined with ICIs." Hong Jae Chon, M.D., Ph.D., the principal investigator, said, "Specifically in renal cell carcinoma, hepatocellular carcinoma, anti-PD-1/CTLA-4 combination is becoming standard-of-care, so combining STB-C017 on top of those combination could yield impressive treatment enhancement."

"The result showed significant feasibility of subsequent development for STB-C017. When the STB-C017 reach market, those ICIs would be used more broadly, which would give us the opportunity," said Sunil Youn, M.D., Business Development Director of Syntekabio.

The presentation with key findings is titled "Artificial intelligence with a deep learning technology enables a rational development of a potent immunotherapeutic agent," and includes:

STB-C017 effectively blocked kynurenine secretion from tumor, an immunosuppressor, and showed dose-response relationship in colorectal cancer mice models.
STB-C017 treatment showed significant infiltrations of CD8+ T cells into the tumor, and reduction of Treg Cells.
STB-C017 dosing regimen optimized as 5 days of administration & 2 days off
Combination therapy with anti-PD1/CTLA4 markedly delayed tumor growth and induced multiple CRs.
– STB-C017 triple combination induced two-fold increase of CRs compared to epacadostat triple. Recovered mice acquired long-term antineoplastic immunity.
– Mice treated with STB-C017 triple combination showed marked survival benefit compared to the others, including epacadostat triple.
Syntekabio plans subsequent STB-C017 development, including GLP toxicology and animal PKPD, targeting IND submission, around 1H 2022. The company will execute further translational research based on firm collaboration with CHA Bundang Hospital and lead the full scope of the development programs.

On May 15, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the latest research progress of the company will be presented at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Ascentage Pharma, MAY 15, 2020, View Source [SID1234558192]). Because of concerns about the current coronavirus (COVID-19) pandemic, this year’s AACR (Free AACR Whitepaper) annual meeting is being held in two sessions in a virtual format. The first session was April 27-28, and the second session, in which Asentage Pharma is set to present, will be June 22-24.

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As the most comprehensive and critically important basic-science cancer research meeting in the world, the AACR (Free AACR Whitepaper) annual congress covers the latest discoveries across the spectrum of cancer research.

Ascentage Pharma will report six research results involving multiple cancer types in poster presentations during the meeting. Among them, APG-3526, the company’s newest drug candidate, will be presented for the first time.

"The research results we’re presenting at AACR (Free AACR Whitepaper) represent our further progress in research and development aimed to address unmet clinical needs. The results provide scientific rationale for exploring combination therapies in different mechanisms of action with drug candidates in our apoptosis-targeting pipeline, including APG-2575, APG-115 and APG-1252," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Combination therapy is playing an increasingly important role in cancer treatment. We hope to make more research and development progress and benefit patients sooner."

Development of APG-3526 as a novel and highly efficacious
MCL-1 inhibitor

Abstract: #2349
Background: MCL-1 is an important anti-death BCL-2 family protein and plays a key role in blocking apoptosis in cancer cells. The MCL-1 gene is located in one of the most frequently amplified loci in various hematologic malignancies and solid tumors. MCL-1 overexpression is implicated as a resistance factor for multiple therapies including widely prescribed microtubule-targeted agents for breast cancers. Therefore, MCL-1 is an attractive therapeutic target for the treatment of cancers. This study explored the chemical synthesis optimization and both the potent antiproliferative and antitumor activity of the lead preclinical compound APG-3526 using multiple in vitro and xenograft models.
Results: We have discovered the novel and highly potent MCL-1 selective inhibitor APG-3526, which displays clinically relevant pharmacokinetic properties and elicits potent antiproliferative and antitumor activities via disrupting MCL-1 complex and triggering caspase activation, especially in MCL-1 driven MM models. These results support APG-3526 as a promising MCL-1 inhibitor for further clinical development.
APG-2575, a clinical stage BCL-2 selective inhibitor, sensitizes estrogen receptor-positive breast cancers to
standard therapies in the preclinical models

Abstract: #3472
Background: Breast cancer is a heterogeneous disease with at least four categories according to the presence or absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. In ER⁺ breast cancer, anti-estrogen therapies with tamoxifen, or CDK4/6 plus aromatase inhibitors, remain the standard endocrine therapies, whereas the combination of CDK4/6-targeted therapy plus fulvestrant (an ER degrader) follows when the disease progresses on the hormonal therapy. However, drug resistance to the current therapies frequently emerges. Developing more effective treatments becomes an urgent need. Among four subsets of breast cancer, ER⁺ breast cancer exhibits the highest BCL-2 expression. Thus, inhibition of BCL-2 which triggers apoptosis of cancer cells may become an effective therapy synergizes the current therapies. APG-2575 is a BCL-2 selective inhibitor currently in clinical trials in patients with hematologic malignancies. Here, in preclinical xenograft models of ER+ breast cancer in mice, we evaluated whether APG-2575 enhanced the sensitivity to tamoxifen or CDK4/6-targeted (i.e., palbociclib or palbociclib plus fulvestrant) therapy.
Results: We demonstrated that Combining APG-2575 with tamoxifen or palbociclib therapies substantially enhanced antitumor activity and overcomes tamoxifen resistance in the preclinical models of ER+ breast cancer, suggesting a novel strategy for the clinical development of BCL-2 inhibitors in ER+ breast cancers.
Combination of BCL-2/BCL-xL dual inhibitor APG-1252 and chemotherapeutics overcomes resistance to osimertinib in EGFR mutant NSCLC in preclinical models

Abstract: #3631
Background: Osimertinib (AZD9291) is the first-line treatment for EGFR-mutated non-small-cell lung cancer (NSCLC); however, the majority of patients inevitably develop resistance due to de novo genomic abnormalities, such as C797S mutation, EGFR exon 20 insertion, MET amplification and other unknown mechanisms. Hence, effective therapies to overcome acquired resistance are urgently needed. Inhibition of BCL-2/BCL-xL has been reported to enhance apoptosis in EGFR-TKI resistant cells with low sensitivity to EGFR inhibition. In this study, we evaluated whether the combination of a dual BCL-2/BCL-xL inhibitor APG-1252 and chemotherapeutics could overcome osimertinib resistance in preclinical xenograft models.
Results: Combination therapy with APG-1252 and cisplatin or docetaxel exhibited synergistic antitumor activity. The APG-1252 plus docetaxel combination achieved 100% tumor partial regression (PR). Similar results were demonstrated in a patient-derived xenograft (PDX) tumor model derived from an osimertinib-resistant patient with NSCLC harboring 19del-T790M-C797S mutation. Furthermore, the combinations also exhibited enhanced antitumor activity in an osimertinib-resistant PDX model that the resistant mechanism remained unknown. In summary, these results suggest that the combination treatment with APG-1252 and chemotherapeutics can overcome acquired resistance to osimertinib and the combination deserves further clinical evaluations.
Synergy of tyrosine kinase inhibitor HQP1351 and MDM2-p53 antagonist, APG-115, in preclinical models of FLT3 mutant and TP53 wild-type acute myeloid leukemia

Abstract: #3636
Background: HQP1351 is a novel, orally bioavailable multikinase inhibitor targeting BCR-ABL, KIT, and FLT3. Currently, HQP1351 is in phase II clinical trials in relapsed and refractory chronic myeloid leukemia (CML) patients by targeting BCR-ABL. Besides, HQP1351 inhibits both wild-type and mutant FLT3 in kinase binding assay. APG-115 is another clinical stage, small molecule MDM2 antagonist. In the present study, we explored the antitumor effect of the combination of HQP1351 and APG-115, and the molecular mechanism in FLT3-ITD and TP53 wild-type acute myeloid leukemia (AML) in the preclinical setting.
Results: HQP1351 alone exhibited potent antiproliferative activity in FLT3-ITD-mutant and TP53 wild-type human AML cell lines, with nanomolar IC50 values. In vivo, HQP1351 single agent demonstrated significant antitumor activity evidenced by a markedly reduction of tumor burden and prolonged survival in mice. The activity was enhanced when HQP1351 was combined with APG-115. The combined treatment synergistically downregulated p-FLT3, p-ERK, p-STAT5 and antiapoptotic protein MCL-1, and thus enhanced antitumor effects. Taken together, our data provide scientific rationale for clinical development of the combination of HQP1351 and APG-115 in patients with FLT3-ITD-mutant and TP53-wild-type AML.
Therapeutic potential of IAP inhibitor APG-1387 in combination with PARP- or MEK-targeted therapy, or chemotherapy in pancreatic cancer

Abstract: #3673
Background: Pancreatic cancers are notoriously difficult to treat. While poly(ADP-ribose) polymerase (PARP) and mitogen/extracellular signal-regulated kinase (MEK) inhibitors are making progresses in the clinical development, standard chemotherapy, especially paclitaxel protein-bound particles (AbraxaneÒ) in combination with gemcitabine, remains as the first line in pancreatic cancer treatment. To further explore the targeted patient populations for APG-1387, a genomic biomarker guided avatar mouse trial (n=2) using pancreatic cancer patient-derived xenografts (PDXs) was conducted to evaluate the combination with PARP inhibitor olaparib in PDXs carrying BRCA1/2 mutations, MEK inhibitor trametinib in PDXs carrying KRAS mutations, or gemcitabine plus abraxane in PDXs with various mutation background.
Results: The results suggest that APG-1387 is promising in pancreatic cancer treatment, ascribing to its potential synergistic antitumor effect by combining with either PARP inhibitors in BRCA1/2 mutant or MEK inhibitors in KRAS mutant pancreatic cancers. In the patients resistant to the above combinations, the combination with the standard therapy may be explored. Overall, the preclinical study provides the scientific rationale for the future clinical development of these combinations in patients with pancreatic cancer and distinct genomic alterations.
Co-targeting BCL-xL and HER2 high expression to overcome apoptosis blockade in gastric cancer

Abstract: #5901
Background: Gastric cancer is one of the most prevalent cancers in the East Asia population. The five-year survival rate is approximately 20% globally. The analysis of gene expression data suggests that anti-apoptotic protein BCL-xL may be the oncogenic driver in gastric cancer as its expression levels are much higher than BCL-2. In this study, we investigated if a clinical stage dual BCL-2/BCL-xL inhibitor APG-1252 would elicit therapeutic activity and associated mechanisms using a panel of gastric cancer patient-derived xenograft (PDX) models. Additionally, we explored if the combination with HER2 inhibition could enhance the antitumor activity in HER2⁺ gastric cancer models.
Results: The results demonstrate the on-target antitumor activity of
APG-1252, the potential of BCL-xLhigh as a predictive biomarker, and the resistance mechanism conferred by MCL-1. Furthermore, the data provide a scientific rationale for the combined therapy with BCL-xL and HER2 inhibitors to achieve better clinical outcomes in a subset of HER2⁺ gastric cancers.

On May 15, 2020 IDEAYA Biosciences, Inc. (Nasdaq:IDYA) is an oncology-focused precision medicine company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics (Press release, Ideaya Biosciences, MAY 15, 2020, View Source [SID1234558191]). The company announced publication today of abstracts at the 2020 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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The IDEAYA abstracts were posted online by AACR (Free AACR Whitepaper) (View Source) in advance of the AACR (Free AACR Whitepaper) Virtual Annual Meeting II, which will be held on June 22-24, 2020:

Title: "Analysis of drug combinations with the PKC inhibitor IDE196 support dual MEK and PKC inhibition as a rational combination in metastatic uveal melanoma" (Author: Christian Frey)
Title: "MAT2A Inhibitors decrease growth, increase senescence and p53 stability in MTAP-deleted cancer cells" (Author: Neil Bhola)
Title: "In vitro and in vivo characterization of novel MAT2A allosteric inhibitors" (Author: Zhonghua Pei)
IDE196 is a potent and selective protein kinase C (PKC) inhibitor being evaluated in an ongoing Phase 1/2 tumor-agnostic clinical trial in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) hotspot mutations. IDEAYA is currently enrolling into a Phase 2 monotherapy expansion arm for patients with such GNAQ/11 mutant tumors, including Cutaneous Melanoma, and recently completed enrollment into a Phase 1 monotherapy arm for patients with Metastatic Uveal Melanoma. IDEAYA is preparing to evaluate the clinical combination of IDE196 and binimetinib, a MEK inhibitor, in a combination arm initiating in mid-2020 for patients with such GNAQ/11 hotspot mutations.

"We believe that IDE196 presents multiple opportunities for being impactful for patients and creating value. The preclinical combination data with IDE196 and MEK inhibitor being presented at AACR (Free AACR Whitepaper) helps guide our clinical development strategy, and demonstrates our commitment to validating these opportunities," said Yujiro S. Hata, Chief Executive Officer and President at IDEAYA Biosciences.

IDEAYA’s most advanced synthetic lethality program is targeting methionine adenosyltransferase II alpha (MAT2A). IDEAYA plans to develop a MAT2A inhibitor for patients having solid tumors with methylthioadenosine phosphorylase (MTAP) gene deletion, which occurs in approximately 15% of all solid tumors. MTAP-null tumor cells have been shown to be more dependent on the activity of MAT2A, resulting in synthetic lethality when MAT2A is pharmacologically inhibited.

"We are building a leading company in synthetic lethality – an emerging area of precision medicine oncology, with active ongoing research across multiple targets, including MAT2A, Pol theta, Werner helicase and PARG. Our MAT2A program presents a potential opportunity to be best in class in the molecularly-defined patient population of MTAP-deletion. We recently selected a differentiated MAT2A inhibitor lead compound and are on track for an IND submission to the FDA in the fourth quarter of 2020. We look forward to sharing additional data on this molecule as we advance this program," said Dr. Michael Dillon, Ph.D., Senior Vice President, Chief Scientific Officer and Head of Research at IDEAYA Biosciences.

On May 15, 2020 Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, reported its recent accomplishments and financial results for the quarter ended March 31, 2020 (Press release, Soligenix, MAY 15, 2020, View Source [SID1234558190]).

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Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix stated, "This has been a very rewarding year for us thus far. Our pivotal Phase 3 FLASH (Fluorescent Light Activated Synthetic Hypericin) trial continues to demonstrate SGX301’s potential to be an important new treatment for early-stage cutaneous T-cell lymphoma (CTCL). In the double-blind, placebo controlled Cycle 1 portion of the study, a statistically significant treatment response (p=0.04) was achieved in the primary endpoint after 6 weeks of therapy. This positive treatment response continued to significantly improve with extended SGX301 treatment in the open-label treatment cycle, referred to as Cycle 2, with an additional 6 weeks of therapy (p<0.0001 compared to placebo and p<0.0001 compared to 6-weeks treatment). We also continue to advance our pivotal Phase 3 clinical trial of SGX942 (dusquetide) for the treatment of oral mucositis in patients with head and neck cancer (HNC) receiving chemoradiation therapy. Following the positive recommendation received from the independent Data Monitoring Committee, we have successfully achieved our target of 260 patients randomized into the study; however, due to the uncertainty surrounding the coronavirus pandemic, we decided to enroll up to 25 additional patients into the study. We are taking this cautious approach in order to maintain the statistical integrity of the trial, by accounting for patients that may potentially drop out of the study before completing their protocol required study treatment and evaluations. Therefore, the study target to complete enrollment and provide top-line results has been revised to the fourth quarter 2020; however, this will continue to remain dependent on the medical and logistical challenges caused by the coronavirus showing a reasonable level of improvement in the relative near-term."

Dr. Schaber continued, "Under our Public Health Solutions business segment, we continue to advance our work with University of Hawaiʻi at Mānoa (UH Mānoa) on filovirus vaccines (protecting against viruses such as Ebola and Marburg) and the development of vaccines to potentially combat coronaviruses, including SARS-CoV-2, the cause of COVID-19. We continue to support our heat stable ricin vaccine, RiVax, with a National Institute of Allergy and Infectious Disease contract award of $21.2 million. With over $8M in cash, not including our non-dilutive government funding, along with the at-the-market sales issuance agreement with B. Riley FBR, Inc. to judiciously supplement our cash runway as needed, we anticipate having sufficient capital to achieve multiple inflection points across our rare disease pipeline, including top-line results in our SGX942 Phase 3 clinical trial in oral mucositis."

Soligenix Recent Accomplishments

On May 11, 2020, the Company announced publication of immunogenicity studies for RiVax identifying novel correlates of immune protection to facilitate potential approval under the United States Food and Drug Administration (FDA) "Animal Rule." The article, titled "A Multivariate Model Combining Endpoint and Epitope-specific Antibody Responses as a Correlate of Protection to Ricin Toxin," has been submitted to the peer-reviewed medical journal Vaccine and a preprint is available here. To view this press release, please click here.
On May 7, 2020, the Company announced that it had received approximately $840,000, net of transaction costs, in non-dilutive financing via the State of New Jersey’s Technology Business Tax Certificate Transfer Program. To view this press release, please click here.
On April 30, 2020, the Company announced that continued treatment with SGX301 (synthetic hypericin) twice weekly for 12 weeks increased the positive response rate to 40% (p<0.0001 compared to placebo and p<0.0001 compared to 6-weeks treatment) in Cycle 2 of its pivotal Phase 3 FLASH study for the treatment of early-stage CTCL. These highly statistically significant results confirm the benefit of continued SGX301 treatment in CTCL patients. To view this press release, please click here.
On April 16, 2020, the Company announced it had executed an agreement for the exclusive worldwide license of CoVaccine HT, a novel vaccine adjuvant, from BTG Specialty Pharmaceuticals, a division of Boston Scientific Corporation (NYSE: BSX), for the fields of pandemic flu and coronaviruses, including SARS-CoV-2, the cause of COVID-19. To view this press release, please click here. This collaboration further builds on the recently announced collaboration between the UH Mānoa and Soligenix to develop a SARS-CoV-2 vaccine (available here).
On April 6, 2020, the Company announced that the European patent office has granted the divisional patent application titled "Formulations and Methods of Treatment of Skin Conditions" (No. 2932973). The granted claims are directed to the therapeutic use of synthetic hypericin in the treatment of CTCL. To view this press release, please click here.
Financial Results – Quarter Ended March 31, 2020

Soligenix’s revenues for the quarter ended March 31, 2020 were $0.9 million as compared to $1.1 million for the quarter ended March 31, 2019. Revenues included payments on a contract in support of RiVax, our ricin toxin vaccine candidate, grants received to support the development of SGX943 for treatment of emerging and/or antibiotic-resistant infectious diseases, ThermoVax, our thermostabilization technology, and the assessment of SGX942 safety in juvenile animals.

Soligenix’s basic net loss was $7.6 million, or ($0.32) per share, for the quarter ended March 31, 2020, as compared to $1.6 million, or ($0.09) per share, for the quarter ended March 31, 2019. This increase in net loss was primarily the result of the issuance of $5 million of common stock as a milestone payment triggered by the successful Phase 3 clinical trial of SGX301 for the treatment of CTCL and increased research and development spending. The number of shares of common stock issued as a milestone payment was calculated using an effective price of $2.56 per share, based upon a formula set forth in the applicable agreement.

Research and development expenses were $2.7 million as compared to $1.6 million for the quarters ended March 31, 2020 and 2019, respectively. The increase in research and development spending for the quarter ended March 31, 2020 was primarily attributable to the site and patient fees for the pivotal Phase 3 clinical trials of SGX301 and SGX942, compared to the same period in 2019.

General and administrative expenses were $0.9 million for both the three months ended March 31, 2020 and 2019.

As of March 31, 2020, the Company’s cash position was approximately $7.2 million, not including the approximate $840,000 recently received from the State of New Jersey’s Technology Business Tax Certificate Transfer Program.

On May 15, 2020 ESSA Pharma Inc. (Nasdaq: EPIX; TSX-V: EPI), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported new preclinical data on ESSA’s clinical candidate, EPI-7386, at the 2020 Virtual American Urological Association ("AUA") Annual Meeting (Press release, ESSA, MAY 15, 2020, View Source [SID1234558189]).

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In an oral poster presentation titled, "The preclinical characterization and development of EPI-7386, an N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer", a more in-depth preclinical characterization of EPI-7386 including gene expression analyses and the toxicologic profile was presented. The studies highlight new information about EPI-7386 including:

In vitro cellular gene expression analyses demonstrate that EPI-7386:
Inhibits androgen-induced genes with major similarities but some differences from enzalutamide in a cellular model sensitive to androgen receptor inhibitors.
In the same cellular model, the combination of enzalutamide and EPI-7386 inhibits androgen-induced gene expression more completely and broadly.
EPI-7386 shows superiority to enzalutamide in inhibiting androgen-induced genes in an androgen receptor resistant model, and in contrast to enzalutamide, also blocks genes induced by the AR-V7 androgen receptor splice variant.
Toxicology studies evaluating the safety profile of EPI-7386 demonstrate that:
Very high plasma exposures of EPI-7386 were achieved across all studies.
The drug was well tolerated at both the low and middle doses, corresponding to drug plasma exposures 2-5 fold higher than the efficacious exposures achieved in mouse xenograft models.
The highest doses tested were characterized as the HNSTD (highest non-severely toxic dose) and only exhibited body weight loss and reduced food consumption. The drug plasma exposures achieved at this high dose were 7-10 fold higher than the efficacious exposures achieved in mouse xenograft models.
The starting clinical dose of EPI-7386 will be 200 mg given once-daily
"The breadth of in vitro and in vivo studies utilized to profile EPI-7386 preclinically demonstrate an encouraging profile for EPI-7386 across a variety of antiandrogen sensitive and antiandrogen-resistant cellular models, xenograft and patient-derived xenograft mouse models, and gene expression analyses. The favorable toxicologic profile of EPI-7386 observed in our IND-enabling studies at very high exposures will permit initiation of the Phase 1 study at a dose of 200 mg per day, which should allow us to reach biologically relevant blood levels of EPI-7386 in patients quickly," said Dr. David R. Parkinson, President & Chief Executive Officer. "We look forward to beginning patient dosing soon in our initial phase 1 study of EPI-7386 in mCRPC patients whose tumors are progressing on current anti-androgens.".