On May 15, 2020 Trillium Therapeutics Inc. ("Trillium" or the "Company") (NASDAQ/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported financial and operating results for the three months ended March 31, 2020 (Press release, Trillium Therapeutics, MAY 15, 2020, View Source [SID1234558205]).

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"We had another strong quarter and are off to a great start in 2020," said Jan Skvarka, Trillium’s President and Chief Executive Officer. "We reported encouraging data for our novel CD47 checkpoint inhibitors TTI-621 and TTI-622, raised $117 million in funding from leading healthcare investors, and made substantial progress by advancing our ongoing TTI-621 and TTI-622 dose escalation studies. At the same time, the first quarter presented its own unique challenges as we navigated the COVID-19 pandemic. In spite of these challenges, we continue to execute on our key strategic objectives, and all employees remain healthy and safe. We continue to benefit from the restructuring of the Company’s footprint and resetting of our strategy in 2019."

First Quarter 2020 Business Highlights:

COVID-19 Pandemic and Business Continuity

In March, Trillium instituted a no-travel and work-from-home policy for all employees, with certain exceptions for lab personnel who analyze perishable patient samples from ongoing clinical studies.
Clinical development studies are ongoing and all active patients are continuing on treatment. Enrollment remains open, although the pace of enrollment is expected to be slower for an uncertain period due to COVID-19 related restrictions and patient risks.
Trillium has sufficient drug supply inventory to complete its ongoing dose escalation studies. The Company has not experienced any disruptions in its drug supply chain to date, but is monitoring closely.
Clinical Development

On January 7, Trillium provided a data update on the ongoing dose escalation studies. The data confirmed TTI-621’s unique monotherapy activity, as well as TTI-622’s strong safety profile.
Dose escalation for TTI-621 is ongoing and the study is currently enrolling patients in the 1.4 mg/kg cohort. This dosing level represents seven times the dose level (0.2 mg/kg) at which initial signal of single agent activity was observed.
The TTI-622 dose escalation study is currently dosing at 8.0 mg/kg. An update of this study will be presented by Dr. Krish Patel of Swedish Cancer Institute on behalf of the study investigators at the "Developmental Therapeutics-Immunotherapy" session of the ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program being held on May 29-31.
Fundraising and Cash Available

On January 28, Trillium closed a public offering for gross proceeds of $117 million.
As of March 31, 2020, the Company had $135 million in cash, cash equivalents and marketable securities, which provides a cash runway into 2022.
First Quarter 2020 Financial Results:
As of March 31, 2020, Trillium had cash and cash equivalents and marketable securities, and working capital of $135.1 million and $115.2 million, respectively, compared to $22.7 million and $9.8 million, respectively at December 31, 2019. The increase in cash and cash equivalents and marketable securities, and the increase in working capital were due mainly to proceeds from the underwritten public offering completed in January 2020 and exercise of warrants.

Net loss for the three months ended March 31, 2020 of $70.1 million was higher than the loss of $8.0 million for the three months ended March 31, 2019, due mainly to revaluation losses recorded on the warrant liability and deferred share unit ("DSU") liability of $55.2 million and $9.3 million respectively, as a result of a higher common share price at March 31, 2020 than at December 31, 2019. In the prior year period, recoveries of $0.5 million and $0.4 million were recorded relating to the fair valuation of the warrant liability and DSU liability, respectively. The revaluation losses in the current period were partially offset by lower clinical trial, manufacturing, intangible assets amortization, share-based compensation, and salary expenses, as well as a lower net foreign currency loss.

Trillium’s outstanding warrants are a non-cash liability, and revaluation losses on the Company’s warrant liability balance are of a non-cash nature. The current DSU plan allows for only cash-settlement of DSUs that are redeemed by directors when their service ends with the Company. To conserve the use of cash for operations, the board of directors has approved the 2020 Omnibus Incentive Plan that provides for equity settlement of DSUs and all directors have agreed to have their existing DSUs administered under the terms of the new plan. Accordingly, all outstanding DSUs issued for director compensation will become equity-settled and classified as equity instead of as a liability, subject to shareholder approval of the 2020 Omnibus Incentive Plan at the Annual General and Special Meeting to be held on June 30, 2020.

On May 15, 2020 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported poster presentations related to AUTO5 in T cell lymphoma and AUTO6NG in small cell lung cancer, as well as an oral presentation related to AUTO7 in prostate cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II on Jun 22 – 24, 2020 (Press release, Autolus, MAY 15, 2020, View Source [SID1234558204]).

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Oral Presentation Title: AUTO7: Anti-PSMA humanized CAR T cell with improved persistence and resistance to tumor microenvironment for metastatic castration resistant prostate cancer (mCRPC)
Session Title: Mini-symposium; MS.IM02.01 – Adoptive Cell Therapy
Abstract: 1070
Date & Time: June 23, 2020, 9:00 AM – 10:30 AM
Presenter: Dr Marco Della Peruta, Senior Scientist II, Immunobiology, Autolus Therapeutics

Poster Presentation Title: AUTO6NG overcomes immune suppressive mechanisms in the TME and demonstrate preclinical anti-tumor activity in GD2-expressing solid tumors
Poster Session Title: Poster Session; PO.TB06.05 – Immune Cells in the Tumor Microenvironment 2
Poster: 2661 / 9
Date & Time: June 22, 2020, 9:00 AM – 6:00 PM
Presenter: Dr Muhammad Al-Hajj, Senior Vice President, Translational Sciences, Autolus Therapeutics

Poster Presentation Title: Targeting TRBC1 and 2 for the treatment of T cell lymphomas
Poster Session Title: Poster Session; PO.IM02.02 – Adoptive Cell Therapy 2
Poster: 2183 / 15
Date & Time: June 22, 2020, 9:00 AM – 6:00 PM
Presenter: Dr Mathieu Ferrari, Associate Director of Binder Discovery, Autolus Therapeutics

Investor call on Thursday June 25, 2020
Management will host a conference call and webcast at 8:30 am EDT/1:30 pm BST to discuss the AACR (Free AACR Whitepaper) data. To listen to the webcast and view the accompanying slide presentation, please go to: View Source

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.