On June 22, 2020 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," "MTEM" or the "Company"), a clinical-stage biopharmaceutical company focused on the discovery and development of the Company’s proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs), reported that four poster presentations featuring pre-clinical data on its pipeline programs are being presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting 2020, being held June 22-24, 2020 (Press release, Molecular Templates, JUN 22, 2020, View Source [SID1234561317]). Copies of the posters presented at AACR (Free AACR Whitepaper) can be found in the Presentations section of Molecular Templates’ website at View Source MTEM also announced an update on its ongoing Phase I study of MT-5111 in HER2-positive cancers.

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Poster Title: In Vivo Efficacy of a PD-L1 Targeted, Antigen Seeding Engineered Toxin Body

Authors: Hilario J. Ramos, Brigitte Brieschke, Sara LeMar, Joseph D. Dekker, Aimee Iberg, Garrett L. Robinson, Asis Sarkar, Banmeet Anand, Melissa M. Singh, Jay Zhao, Jack P. Higgins, Erin K. Willert. Molecular Templates Inc., Austin, TX
MT-6402 is a unique agent designed to deplete tumor and repressive immune cells in the tumor microenvironment. It has multiple unique mechanisms of action that may provide greater potency than is seen with current PD-L1 antibodies. MT-6402 was shown to have potent in vitro activity against a variety of PD-L1+ tumor cells and results in tumor growth delay and survival benefits in NSCLC PDX in vivo model. MT-6402 can alter the immunophenotype of the tumor and allow for recognition by effector T cells. Non-human primate (NHP) data show that MT-6402 mediated PD-L1+ immune cell clearance can elicit highly potent monotherapy immune activation in a way that has not been seen previously in NHP models with checkpoint inhibitors. MT-6402 is slated for IND filing in 2H20.

Poster Title: CTLA-4 Targeted Engineered Toxin Bodies Designed to Deplete Regulatory T Cells (Tregs)

Authors: Aimee Iberg, Edith Acquaye-Seedah, Lilia A. Rabia, Garrett L. Robinson, Hilario J. Ramos, Joseph D. Dekker, Jay Zhao, Erin K. Willert. Molecular Templates Inc., Austin, TX
Tumor resident regulatory T cells (Tregs) are important mediators of an immunosuppressive tumor microenvironment (TME) promoting tumor immune evasion. The presence of Tregs, and a higher ratio of Tregs to effector T cells in the TME, are associated with poor prognosis. There is concern that antibodies to CTLA-4 are not sufficiently effective at clearing Tregs from the TME. ETBs are being developed to specifically target CTLA-4+ Tregs and clear them from the TME. Because CTLA-4-targeted ETBs preferentially affect Tregs versus CTLA-4+ CD8 T-cells, ETBs may also have a safer profile than CTLA-4 antibodies. In co-culture models CTLA-4 ETBs were shown to relieve Treg suppression of T-effector proliferation. Experiments in mice showed that CTLA-4 ETB 1 (as labeled on the AACR (Free AACR Whitepaper) poster) displays a short serum half-life and is well tolerated in vivo. An IND for a CTLA-4 ETB is expected to be filed in 2021.

Poster Title: Novel Engineered Toxin Bodies Targeting SLAMF7 (CS1)

Authors: Aimee Iberg, Garrett L. Cornelison, Caleigh Howard, Garrett L. Robinson, Jay Zhao, Hilario J. Ramos, Erin K. Willert. Molecular Templates Inc., Austin, TX
SLAMF7 (CS1) is a clinically validated target of monoclonal antibody therapy for the treatment of multiple myeloma. The approved antibody-based therapeutic, elotuzumab, works indirectly by recruiting effector cells to the tumor but does not show single agent clinical activity. ETBs have the potential to deplete malignant cells by means of potent and direct cell kill through enzymatic ribosomal destruction. SLAMF7 ETBs were shown to be active alone and in the presence of elotuzumab. Epitopes distinct from elotuzumab are options for ETB engagement, allowing activity in the presence of elotuzumab. SLAMF7 ETBs combine with standard of care chemotherapy (IMiDs) and bortezomib in a positive manner in vitro. Lead selection is underway with the testing of various ETB scaffolds and additional binding domains targeting multiple SLAMF7 epitopes.

Poster Title: CD45 Targeted Engineered Toxin Bodies Deplete Hematopoietic and Malignant Cells

Authors: Aimee Iberg, Garrett L. Robinson, Sara LeMar, Joseph D. Dekker, Jay Zhao, Hilario J. Ramos, Melissa M. Singh, Erin K. Willert. Molecular Templates Inc., Austin, TX
CD45, the leucocyte common antigen, is a haemopoietic cell-specific tyrosine phosphatase. Targeted and potent ETBs with intrinsically short half-lives are being developed to specifically destroy CD45 expressing cells including malignant cells of B, T and myeloid lineage. A single agent, targeted conditioning method for bone marrow transplant (BMT), employing ETBs, has the potential to increase patient safety and eliminate genotoxic effects that are associated with existing conditioning regimens. Antibody discovery campaigns have the potential to direct ETBs to specific isoforms of CD45 for refinement of indications including various cancers and autoimmune diseases.

Update on Phase I study of MT-5111

MT-5111, a HER2 targeted ETB, is in an ongoing Phase 1 study that has two parts: Part 1 is dose escalation and Part 2 is dose expansion, which will begin when a maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) is established in Part 1. To date, 10 subjects, with a median of 5 prior lines of therapy and a median of 2 prior HER2-targeting regimens, have been treated with MT-5111 (metastatic cholangiocarcinoma n=5, metastatic breast cancer n=4, metastatic gastro-esophageal junction carcinoma n=1). Thus far, no dose limiting toxicities (DLTs) have been observed in any cohort and MT-5111 appears to be well tolerated, with no cardiotoxicity to date (cardiotoxicity is a known potential toxicity for HER2 targeted therapies).

Currently there are 4 subjects in total on treatment from the second (1 μg/kg/dose) and third cohorts (2 μg/kg/dose). No cardiac AEs or abnormalities in cardiac biomarkers have been noted thus far. Reported AEs that may be causally related among the 3 cohorts to date include the following: one instance of grade 1 chills, one instance of grade 1 hypophosphatemia, one instance of grade 1 nausea, and one instance of grade 2 AST elevation. The grade 2 AST elevation occurred in a subject in cohort 1 with disease progression in hepatic metastases; no causally related AST or ALT elevations have been noted in any other subjects to date. The ongoing subject from cohort 2 (45 y/o female with metastatic breast cancer) has stable disease (the subject only has evaluable disease but no measurable lesions per RECIST 1.1, and is classified as non-CR, non-PD per protocol) and remains on treatment, now in cycle 5. One subject in cohort 3 with metastatic breast cancer has had a follow-up CT scan at the end of cycle 2 and has stable disease. Six subjects have discontinued for disease progression and two subjects are too early to evaluate. Cohort 4 (3.0 μg/kg/dose) is anticipated to open shortly. Molecular Templates is encouraged by the safety profile to date in these heavily pretreated patients and expects to provide an update on results from the patients currently on treatment as well as higher dose cohorts from the dose escalation portion of the Phase 1 study (including doses that are predicted to be clinically active based on preclinical data) in 4Q20.

Conference Call and Webcast to Discuss AACR (Free AACR Whitepaper) Posters

Molecular Templates will host a live webcast and conference call in Eric Poma, Ph.D., Molecular Templates’ Chief Executive Officer and Scientific Officer, will provide an update on the Company’s pipeline programs and discuss the four abstracts presented at AACR (Free AACR Whitepaper).

On June 22, 2020 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) reported that Health Canada has authorized QINLOCK (ripretinib), a switch-control tyrosine kinase inhibitor, for sale in Canada for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with imatinib, sunitinib, and regorafenib (Press release, Deciphera Pharmaceuticals, JUN 22, 2020, View Source [SID1234561316]). The QINLOCK New Drug Submission was approved by Health Canada under Project Orbis, an initiative of the U.S. Food and Drug Administration’s (FDA) Oncology Center of Excellence designed to provide a framework for concurrent submission and review of oncology products among international partners. In May 2020, QINLOCK was approved by the U.S. FDA for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

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"Health Canada’s authorization of QINLOCK as part of FDA’s Project Orbis marks an important milestone for GIST patients who have long awaited a new therapeutic option specifically designed to address this complex disease," said Steve Hoerter, President and Chief Executive Officer of Deciphera. "We would like to thank Health Canada for their collaboration during the review process and we look forward to bringing this important new therapy to patients in Canada."

Health Canada’s authorization was based on efficacy results from the pivotal Phase 3 INVICTUS study of QINLOCK in patients with advanced GIST as well as combined safety results from INVICTUS and the Phase 1 study of QINLOCK. In INVICTUS, QINLOCK demonstrated a median progression-free survival of 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001). In addition, QINLOCK demonstrated a median overall survival of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).

The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (PPES), and vomiting. Adverse reactions resulting in permanent discontinuation occurred in 8% of patients, dosage interruptions due to an adverse reaction occurred in 24% of patients and dose reductions due to an adverse reaction occurred in 7% of patients who received QINLOCK.

About the INVICTUS Phase 3 Study

INVICTUS is a Phase 3 randomized, double-blind, placebo-controlled, international, multicenter clinical study evaluating the safety, tolerability, and efficacy of QINLOCK compared to placebo in patients with advanced GIST whose previous therapies have included imatinib, sunitinib, and regorafenib. Patients were randomized 2:1 to either 150 mg of QINLOCK or placebo once daily. The primary efficacy endpoint is progression-free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). The median PFS in the study was 6.3 months compared to 1.0 month in the placebo arm and significantly reduced the risk of disease progression or death by 85% (hazard ratio of 0.15, p<0.0001). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR) and Overall Survival (OS). QINLOCK demonstrated an ORR of 9.4% compared with 0% for placebo (p =0.0504). QINLOCK also demonstrated a median OS of 15.1 months compared to 6.6 months in the placebo arm and reduced the risk of death by 64% (hazard ratio of 0.36).

About QINLOCK (ripretinib)

QINLOCK is a tyrosine kinase switch control inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. QINLOCK inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18 involved in GIST, as well as the primary exon 17 D816V mutation involved in SM. QINLOCK also inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, involved in a subset of GIST.

QINLOCK is approved by the U.S. FDA for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib, and by Health Canada for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with imatinib, sunitinib, and regorafenib.

Deciphera Pharmaceuticals is developing QINLOCK for the treatment of KIT and/or PDGFRα-driven cancers, including GIST, systemic mastocytosis, or SM, and other cancers. Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of QINLOCK in Greater China (Mainland China, Hong Kong, Macau, and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for QINLOCK in the rest of the world.

U.S. Indication and Important Safety Information About QINLOCK

Indications and Usage

QINLOCK (ripretinib) is a kinase inhibitor indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib. For more information visit QINLOCK.com.

Important Safety Information

There are no contraindications for QINLOCK.

Palmar-plantar erythrodysesthesia syndrome (PPES): In INVICTUS, Grade 1-2 PPES occurred in 21% of the 85 patients who received QINLOCK. PPES led to dose discontinuation in 1.2% of patients, dose interruption in 2.4% of patients, and dose reduction in 1.2% of patients. Based on severity, withhold QINLOCK and then resume at same or reduced dose.

New Primary Cutaneous Malignancies: In INVICTUS, cutaneous squamous cell carcinoma (cuSCC) occurred in 4.7% of the 85 patients who received QINLOCK with a median time to event of 4.6 months (range 3.8 to 6 months). In the pooled safety population, cuSCC and keratoacanthoma occurred in 7% and 1.9% of 351 patients, respectively. In INVICTUS, melanoma occurred in 2.4% of the 85 patients who received QINLOCK. In the pooled safety population, melanoma occurred in 0.9% of 351 patients. Perform dermatologic evaluations when initiating QINLOCK and routinely during treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Continue QINLOCK at the same dose.

Hypertension: In INVICTUS, Grade 1-3 hypertension occurred in 14% of the 85 patients who received QINLOCK, including Grade 3 hypertension in 7% of patients. Do not initiate QINLOCK in patients with uncontrolled hypertension. Monitor blood pressure as clinically indicated. Based on severity, withhold QINLOCK and then resume at same or reduced dose or permanently discontinue.

Cardiac Dysfunction: In INVICTUS, cardiac failure occurred in 1.2% of the 85 patients who received QINLOCK. In the pooled safety population, cardiac dysfunction (including cardiac failure, acute left ventricular failure, diastolic dysfunction, and ventricular hypertrophy) occurred in 1.7% of 351 patients, including Grade 3 adverse reactions in 1.1% of patients.

In INVICTUS, Grade 3 decreased ejection fraction occurred in 2.6% of the 77 patients who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram. Grade 3 decreased ejection fraction occurred in 3.4% of the 263 patients in the pooled safety population who received QINLOCK and who had a baseline and at least one post-baseline echocardiogram.

In INVICTUS, cardiac dysfunction led to dose discontinuation in 1.2% of the 85 patients who received QINLOCK. The safety of QINLOCK has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or MUGA scan prior to initiating QINLOCK and during treatment, as clinically indicated. Permanently discontinue QINLOCK for Grade 3 or 4 left ventricular systolic dysfunction.

Risk of Impaired Wound Healing: QINLOCK has the potential to adversely affect wound healing. Withhold QINLOCK for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of QINLOCK after resolution of wound healing complications has not been established.

Embryo-Fetal Toxicity: QINLOCK can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for at least 1 week after the final dose. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment and for at least 1 week after the final dose. QINLOCK may impair fertility in males of reproductive potential.

Adverse Reactions: The most common adverse reactions (≥20%) were alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, PPES, and vomiting. The most common Grade 3 or 4 laboratory abnormalities (≥4%) were increased lipase and decreased phosphate.

The safety and effectiveness of QINLOCK in pediatric patients have not been established.

Administer strong CYP3A inhibitors with caution. Monitor patients who are administered strong CYP3A inhibitors more frequently for adverse reactions. Avoid concomitant use with strong CYP3A inducers.

Please click here to see the full U.S. Prescribing Information for QINLOCK.

About GIST

Gastrointestinal stromal tumor (GIST) is a cancer affecting the digestive tract or nearby structures within the abdomen, most often presenting in the stomach or small intestine. GIST is the most common sarcoma of the gastrointestinal tract, with approximately 4,000 to 6,000 new GIST cases each year in the United States and a similar incidence rate in European and other countries. Most cases of GIST are driven by a spectrum of mutations. The most common primary mutations are in KIT kinase, representing approximately 80% of cases, or in PDGFRα kinase, representing approximately 6% of cases. Current therapies are unable to inhibit the full spectrum of primary and secondary mutations, which drives resistance and disease progression. Estimates for 5-year survival range from 48% to 90%, depending on the stage of the disease at diagnosis.

On June 22, 2020 Ribon Therapeutics, a clinical stage oncology company developing first-in-class therapeutics targeting stress response pathways, reported new data to be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting II, taking place from June 22-24, 2020 (Press release, Ribon Therapeutics, JUN 22, 2020, View Source [SID1234561315]).

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"PARP7 is a fundamental regulator of intrinsic stress support pathways and represents a novel cancer cell vulnerability," said Heike Keilhack, Ph.D., Senior Vice President of Biological Sciences, Ribon Therapeutics. "RBN-2397 is the first potent and selective inhibitor of PARP7 and exhibits potent anti-tumor activity as a monotherapy, as well as in combination with other therapies, including immune checkpoint inhibitors."

"The posters presented at AACR (Free AACR Whitepaper) provide a glimpse into Ribon’s unique ability to interrogate the complex biology of stress support pathways to identify novel therapeutic targets," said Kevin Kuntz, Ph.D., Senior Vice President of Molecular Discovery, Ribon Therapeutics. "The multi-dimensional, in silico mining tools and bespoke screening assays Ribon has developed were instrumental in the identification of PARP7 and RBN-2397 and are critical components of the platform, which we have assembled to validate new monoPARP and NADase targets and develop novel therapeutics."

Ribon will present the following from its development program and platform:

Abstract Title: PARP7 negatively regulates the Type I interferon response in cancer cells and its inhibition leads to tumor regression
Abstract ID: 3405
Session Type: Minisymposium (oral presentation)
Session Category: Experimental and Molecular Therapeutics
Session Title: Novel Mechanisms Enabled by Tool Molecules
Date/Time: June 23, 2020, 9:00 – 11:00 a.m. EDT
Presenter: Joseph M. Gozgit, Ph.D.
Summary:

Data demonstrate that cancer cells use PARP7 to suppress the Type I IFN response to cytosolic nucleic acids. RBN-2397, a first-in-class, potent and selective inhibitor of PARP7 is shown to restore Type I IFN signaling in the tumor and cause complete tumor regressions and adaptive immunity in murine models.
Targeting cytosolic nucleic acid sensing pathways and the Type I interferon (IFN) response is an emerging therapeutic strategy being explored in oncology. PARP7 expression is increased by cellular stress and aromatic hydrocarbons, and the PARP7 gene is amplified in cancers, especially in those of the upper aerodigestive tract. PARP7 has also been reported to negatively regulate the Type I IFN response by interacting with TBK1 during viral infection. PARP7 is identified as a novel negative regulator of cytosolic nucleic acid sensing in tumor cells.
Title: A bespoke screening platform to study mono(ADP-ribosylation)
Abstract ID: 506 / 2
Session Type: Poster Session
Session Title: Screening, Lead Identification, and Optimization
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Tim J. Wigle, Ph.D.
Summary:

Development of robust, high-throughput biochemical and cellular monoPARP assays that overcome the lack of knowledge around the substrates and construction of a family-wide screening panel. These assays have been used in high-throughput screening campaigns, as well as in the development of potent and selective inhibitors of multiple monoPARP enzymes, including cell active chemical probes for PARP3, PARP7, PARP10, PARP12, PARP14 and PARP16.
Title: A multi-omic characterization of PARP enzymes in cancer to identify novel monoPARP drug targets
Abstract ID: 4381
Session Type: Poster Session
Session Title: Knowledge, Networks, Graphs, and Models for Discovery
Date/Time: June 22, 2020, 9:00 a.m. – 6:00 p.m. EDT
Presenter: Ryan Abo, Ph.D.
Summary:

The first pan-cancer in silico characterization of the PARP family, revealing a broad molecular and potential mechanistic diversity among the PARPs across cancer. Notwithstanding the lack of traditional oncogenic features, such as mutational hotspots, in the PARPs, analyses highlight several monoPARPs with potential oncogenic roles and further support our focus of targeting these in the clinic.
AACR Virtual Meeting II the second of two virtual meetings being held by AACR (Free AACR Whitepaper); the first, AACR (Free AACR Whitepaper) Virtual Meeting I, took place April 27-28, 2020. Presentations from Virtual Meeting I can be accessed at View Source

On June 22, 2020 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that new translational data for BT5528 and preclinical data for tumor-targeted immune cell agonists (TICAs) will be presented during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II on June 22-24, 2020 (Press release, Bicycle Therapeutics, JUN 22, 2020, View Source [SID1234561314]).

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"The translational and preclinical data we are presenting at AACR (Free AACR Whitepaper) further inform the potential utility Bicycle-based therapeutic candidates have as a new modality that could shift the treatment paradigm for cancer, among other serious diseases," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "Our fit-for-purpose immunohistochemistry, or IHC, assay was developed for use in the BT5528 Phase I/II trial and is designed to help us maximize our chances of success in the clinic by guiding tumor type selection and patient enrollment criteria. Additionally, the preclinical data we continue to generate for our TICA molecules remains very encouraging, especially as we look to initiate clinical studies of BT7480 next year."

New translational data for BT5528, a second-generation Bicycle Toxin Conjugate (BTC) that targets EphA2, describe the development of Bicycle’s proprietary IHC assay. This assay will be used to support patient selection and assess EphA2 expression levels in tumor samples collected in the ongoing Phase I/II trial of BT5528. EphA2 is a well-known tumor antigen shown to be overexpressed in a range of difficult to treat solid tumor types. While many independent EphA2 IHC assays have been reported, Bicycle’s is the first to specifically detect the extracellular domain of EphA2 and to score its expression at both the tumor cytoplasm and tumor membrane, which is where BT5528 binds.

Bicycle TICAs are potent, fully synthetic compounds that represent an immuno-oncology approach engineered to overcome the limitations of other immunomodulatory mechanisms. At AACR (Free AACR Whitepaper), the Company will present new preclinical data for BT7480, a TICA targeting Nectin-4 and agonizing CD137 (4-1BB), indicating that anti-tumor responses in a syngeneic mouse model can be achieved with an intermittent dosing regimen, which suggests that continuous target coverage may be unnecessary for efficacy. Additional PK/PD and safety data for BT7480 from in vivo mouse and non-human primate models demonstrate potent, target-dependent anti-tumor activity. At dose levels tested, BT7480 has been shown to be well-tolerated in preclinical species, with no signs of toxicity issues associated with other immuno-oncology agonist therapies. IND-enabling activities for BT7480 are ongoing.

New preclinical data for EphA2/CD137 TICAs similarly indicate highly target dependent CD137 agonism, most notably in a syngeneic mouse model that showed robust antitumor activity. Complete responder animals in this model were subsequently re-challenged with the same tumor cell implantation and no tumor growth was observed, implying development of immunogenic memory. In further PK/PD experiments, intermittent plasma exposure of an EphA2/CD137 TICA produced robust anti-tumor activity, again implying continuous target coverage is not required for efficacy. Earlier this year, Bicycle selected BT7455, an EphA2/CD137 TICA, as another Bicycle-based immuno-oncology candidate to advance into clinical studies.

Details on Bicycle’s poster presentations at AACR (Free AACR Whitepaper) are as follows:

Session Title: Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes 2
Session Category: Experimental and Molecular Therapeutics
Poster Title: A survey of EphA2 expression by immunohistochemistry (IHC) in tumor tissue microarrays (TMAs) to support BT5528 indication selection
Abstract #: 3302

Session Title: Immunomodulatory Agents and Interventions 2
Session Category: Immunology
Poster Title: BT7480, a novel fully synthetic tumor-targeted immune cell agonist (TICA) induces tumor localized 4-1BB agonism
Abstract #: 5241

Session Title: Immunomodulatory Agents and Interventions 3
Session Category: Immunology
Poster Title: A fully synthetic EphA2/4-1BB tumor-targeted immune cell agonist (TICA) induces tumor localized 4-1BB agonism
Abstract #: 4613

The posters are available on the Publications section of bicycletherapeutics.com.

On June 22, 2020, Cue Biopharma, Inc. (the "Company") reported that it entered into an At-The-Market Equity Offering Sales Agreement (the "Sales Agreement") with Stifel, Nicolaus & Company, Incorporated, as agent ("Stifel"), pursuant to which the Company may offer and sell, from time to time through Stifel, shares of its common stock, par value $0.001 per share (the "Common Stock"), for aggregate gross proceeds of up to $40.0 million (the "Shares") (Filing, 8-K, Cue Biopharma, JUN 22, 2020, View Source [SID1234561313]). The offer and sale of the Shares will be made pursuant to a shelf registration statement on Form S-3 and the related prospectus (File No. 333-239357) that became effective on June 22, 2020, as supplemented by a prospectus supplement dated June 22, 2020 and filed with the Securities and Exchange Commission pursuant to Rule 424(b) under the Securities Act of 1933, as amended (the "Securities Act").

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Pursuant to the Sales Agreement, Stifel may sell the Shares in sales deemed to be "at-the-market" equity offerings as defined in Rule 415 promulgated under the Securities Act, including sales made directly on or through the Nasdaq Capital Market. If agreed to in a transaction notice, the Company may sell Shares to Stifel as principal, at a purchase price agreed upon by Stifel and the Company. Stifel may also sell Shares in negotiated transactions with the Company’s prior approval. The offer and sale of the Shares pursuant to the Sales Agreement will terminate upon the earlier of (a) the issuance and sale of all of the Shares subject to the Sales Agreement or (b) the termination of the Sales Agreement by Stifel or the Company pursuant to the terms thereof.

The Company has agreed to pay Stifel a commission of up to 3.0% of the aggregate gross proceeds from any Shares sold by Stifel and to provide Stifel with customary indemnification and contribution rights, including for liabilities under the Securities Act. The Company also will reimburse Stifel for certain specified expenses in connection with entering into the Sales Agreement. The Sales Agreement contains customary representations and warranties and conditions to the placements of the Shares pursuant thereto.

A copy of the Sales Agreement is filed as Exhibit 1.1 to this Current Report, and the description of the terms of the Sales Agreement is qualified in its entirety by reference to such exhibit. A copy of the opinion of K&L Gates LLP relating to the legality of the issuance and sale of the Shares is attached as Exhibit 5.1 hereto.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the Shares, nor shall there be any offer, solicitation, or sale of the Company’s Common Stock in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.