On January 8, 2020 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported an update from several clinical development programs and a 2020 business overview (Press release, Bio-Path Holdings, JAN 8, 2020, View Source [SID1234552845]).

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"We enter 2020 with robust development plans to commence several key clinical trials that are expected to advance our DNAbilize antisense RNAi nanoparticle technology in a number of important oncology indications for which there are limited treatment options," said Peter H. Nielsen, President and Chief Executive Officer of Bio-Path. "We are excited to initiate a number of important studies across our development pipeline and anticipate reporting key clinical datapoints from those studies later in the year."

Phase 2 Study of Prexigebersen in Untreated and Refractory/Resistant Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) Patients

In March 2019, Bio-Path announced a revised strategy for the Stage 2 portion of its Phase 2 clinical trial of prexigebersen in combination with frontline chemotherapy. Bio-Path’s amended Stage 2 of the Phase 2 clinical trial will treat two cohorts of patients. The first cohort is to include untreated AML patients as existed in the pre-amended trial but with the addition of untreated, high-risk MDS patients. The second cohort is to include refractory/relapsed AML patients and high-risk MDS patients. Both cohorts of patients are planned to be treated with the combination of prexigebersen, decitabine and venetoclax. The Company is finalizing amendments to add this combination treatment to Stage 2 of the Phase 2 clinical trial.

The first step in the revised strategy involved testing the safety of the combination of prexigebersen and decitabine. In November 2019, the Company announced successful completion of this safety testing in AML and MDS patients in Stage 2 of the Phase 2 clinical study. The safety segment of Stage 2 of the Phase 2 clinical trial comprised six evaluable patients who were treated with the combination of prexigebersen and decitabine. Although the combination of prexigebersen and decitabine is not the treatment currently planned for the efficacy evaluation of Stage 2 of the Phase 2 clinical trial, the efficacy profile in this safety segment of the study was very encouraging, with 50% of patients having a response, including two patients (33%) showing complete responses with incomplete hematologic recovery and one patient (17%) showing partial response. For reference, in this class of AML and MDS patients, the complete response rate to treatment with decitabine alone is approximately 20%. Some patients are continuing to receive treatment.

The next step in this Stage 2 of the Phase 2 program will be the safety testing of prexigebersen in combination with decitabine and venetoclax in six evaluable patients drawn from either of the two cohorts of untreated AML and high-risk MDS patients or relapsed/refractory AML and high-risk MDS patients. The Company currently expects to initiate this safety testing in the second quarter of 2020. Assuming successful completion of this safety testing, the Company plans that it would then initiate the efficacy testing of this triple combination in the two cohorts of patients. In 2020, Bio-Path intends to continue its efforts to expand the number of sites, including European-based sites, to enhance patient enrollment.

The clinical design of the Stage 2 portion of the Phase 2 clinical trial calls for an interim analysis of each cohort’s results after each cohort has treated 19 evaluable patients. If the results from either or both patient cohorts exceed expectations for current standard-of-care therapy, the Company expects that plans for a pivotal trial would be discussed with the FDA.

Phase 2a Study of Prexigebersen to treat Chronic Myeloid Leukemia (CML) in Tyrosine Kinase Inhibitor Failures and Accelerated and Blast Phase CML Patients

Bio-Path plans to enroll patients in a Phase 2a clinical study of prexigebersen in combination with the frontline therapy, dasatinib, for the treatment of CML in tyrosine kinase inhibitor failures and accelerated and blast phase patients in 2020. The trial is expected to be conducted at The University of Texas MD Anderson Cancer Center as a potential salvage therapy for accelerated and blast phase CML patients and will expand to other sites if feasible. Recent advances in the treatment of chronic phase CML patients with tyrosine inhibitors has limited the availability of these patients for the Bio-Path Phase 2a. As a result, the continuation of this study is being evaluated based on the potential for patient availability and clinical trial site expansion. If this Phase 2a study is advanced, it will evaluate two cohorts of three evaluable patients at two doses (60 mg/m2 and 90 mg/m2) of prexigebersen in combination with dasatinib.

Phase 1 Study of Prexigebersen in Patients with Advanced Solid Tumors

In late 2019, Bio-Path filed an Investigational New Drug (IND) application to initiate a Phase 1 clinical trial of prexigebersen in patients with advanced solid tumors, including ovarian and uterine, pancreatic and breast cancer. This trial is expected to commence after the IND has been cleared by the FDA, which we currently anticipate being in 2020, at several leading cancer centers and will evaluate the safety of prexigebersen in these patients. Assuming positive Phase 1 results, the Company expects it would advance to a Phase 1b clinical trial of prexigebersen in combination with frontline therapy in these same advanced solid tumor patients.

Phase 1 Study of BP1002 in Refractory or Relapsed Lymphoma Patients and Chronic Lymphocytic Leukemia Patients

In November 2019 the FDA cleared the IND for BP1002 (liposomal Bcl-2), the Company’s second drug candidate, to begin a Phase 1 clinical trial to evaluate BP1002 as a treatment for refractory/relapsed lymphoma and chronic lymphocytic leukemia patients. This study is expected to commence in the first half of 2020 and is expected to be conducted at several premier oncology centers, including the University of Texas MD Anderson Cancer Center, and is planned to evaluate the safety of BP1002 in several dose escalating cohorts to determine a maximum tolerated dose.

Preclinical Development of BP1003

The Company continues to advance its third investigational drug candidate, BP1003, for the treatment of advanced solid tumors, including pancreatic cancer. BP1003 is an antisense RNAi nanoparticle targeting the Stat3 protein.

In 2020 Bio-Path expects to complete several IND-enabling studies for BP1003. If those studies are successful, Bio-Path expects that it would file an IND in late 2020 for the first-in-humans Phase 1 study of BP1003 in patients with refractory/metastatic solid tumors including pancreatic, non-small cell lung cancer, and colorectal cancers.

BP1003 has demonstrated efficacy in combination with frontline therapies in animals against pancreatic tumors.

On January 8, 2020 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with an extensive pipeline of agents that activate immune response to cancers, reported the dosing of the first patient with AGEN1223 (Press release, Agenus, JAN 8, 2020, View Source [SID1234552844]). AGEN1223 is a novel bi-specific antibody discovered by Agenus and designed to deplete regulatory T cells in the tumor microenvironment. The first patient was infused in December 2019 and the trial is underway with a plan to initiate combinations with balstilimab, Agenus’ investigational PD-1 inhibitor, in 2020.

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Dr. Anthony El-Khoueiry of the USC Norris Comprehensive Cancer Center and Keck School of Medicine was the clinical investigator dosing this first patient. Dr. El-Khoueiry is the phase I program director and a recognized expert in early drug development and translational medicine with a focus in hepatobiliary (liver, gall bladder, and bile duct) and pancreatic cancers.

"AGEN1223 is a novel bispecific antibody designed to selectively deplete specific immune-suppressive cells called regulatory T cells. The ability to deplete these cells in the tumor microenvironment may be an important treatment advantage for patients with cancer," said Dr. Anna Wijatyk, Head of Clinical Development at Agenus. "AGEN1223 is designed to eliminate the escape pathways that tumors use to continue to grow beyond multiple lines of therapy, including anti-PD-1 therapy. We believe that AGEN1223, due to its design to both selectively deplete intratumoral Tregs while sparing peripheral Tregs and to activate effector immune cells, represents an important novel therapy and promising combination agent for patients with aggressive tumors."

The Phase 1, open-label, multicenter study is designed to assess the maximum tolerated dose of AGEN1223 in subjects with advanced solid tumors. It will also evaluate the safety, tolerability, PK, and PD profiles and immunogenicity of this bi-specific antibody.

AGEN1223 was discovered by Agenus scientists and engineered to enhance immune functionality and immunogenicity. Our preclinical data show that AGEN1223 simultaneously engages two antigens that are co-expressed specifically on tumor-infiltrating Tregs thereby prompting their depletion. These data further show that cancer-fighting effector T cells and essential peripheral Tregs, which do not sufficiently co-express these targets, are largely spared from destruction. In addition to its Treg depleting capabilities, AGEN1223 can co-stimulate antigen-specific effector T cells that are essential for tumor killing in preclinical assays. Overall, AGEN1223 may represent a promising combination partner for a range of other therapeutic interventions – which could include checkpoint inhibitors, vaccines, or cell therapy. Gilead Sciences, Inc. has an exclusive option to license AGEN1223 as part of our December 2018 collaboration agreement with the company. Agenus is currently responsible for the development of AGEN1223. AGEN1223 and balstilimab are investigational agents. Their safety and efficacy are being evaluated in a Phase 1 clinical trial.

On January 8, 2020 Acorda Therapeutics, Inc. (NASDAQ: ACOR) reported that Ron Cohen, M.D., Acorda’s President and CEO, will present at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco on Thursday, January 16 at 9:30am PST / 12:30pm EST (Press release, Acorda Therapeutics, JAN 8, 2020, View Source [SID1234552843]).

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A live audio webcast of the presentation can be accessed under "Investor Events" in the Investor section of the Acorda website at www.acorda.com, or you may use the link:

View Source

On January 8, 2020 Veracyte (Nasdaq: VCYT) reported a multi-year partnership with Acerta Pharma, the hematology research and development arm of AstraZeneca (LSE/STO/NYSE: AZN), to provide genomic information that will support the biopharmaceutical company’s development of oncology therapeutics (Press release, Veracyte, JAN 8, 2020, View Source [SID1234552842]). Financial and other terms of the collaboration were not disclosed.

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The agreement marks Veracyte’s first biopharmaceutical partnership since the company announced its acquisition of the exclusive diagnostics rights to the NanoString nCounter platform and genomic tests in breast cancer and lymphoma on December 3, 2019. That transaction positions Veracyte to expand globally using a distributed platform and comprehensive menu of advanced genomic tests.

"We are excited to partner with Acerta Pharma and AstraZeneca, global leaders whose innovative medicines are benefitting millions of patients worldwide," said Bonnie H. Anderson, Veracyte’s chairman and chief executive officer. "This collaboration reflects the significant value we can bring to biopharmaceutical companies through our expanding global footprint, as well as our ability to potentially inform diagnosis and treatment decisions in new oncology indications."

On January 8, 2020 Molecular Templates, Inc., (Nasdaq: MTEM) 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 provided a corporate update and outlined expected 2020 milestones (Press release, Molecular Templates, JAN 8, 2020, View Source [SID1234552841]).

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"2019 was a year of growth for MTEM as we advanced our pipeline programs, established a new collaboration outside of oncology with a premier partner, and strengthened our balance sheet with a successful equity financing," said Eric Poma, Ph.D., Chief Executive and Chief Scientific Officer of Molecular Templates. "As we start 2020, we look forward to generating clinical data from three ongoing Phase 2 studies with MT-3724, an ongoing Phase 1 study for MT-5111, and a Phase 1 study with TAK-169. We expect to file an IND in 2H20 for MT-6402, our PD-L1-targeted ETB with antigen seeding capabilities, and we will continue to advance our earlier stage pipeline while making progress with our existing collaborations."

2019 Accomplishments, Status Updates, and Expected 2020 Milestones

MT-3724 (CD20 ETB)

Candidate description
MT-3724 is a 1st generation ETB that utilizes wild-type Shiga-like toxin A (SLTA) genetically fused to an scFv to CD20 to bind, induce internalization, and destroy CD20-expressing tumor cells through ribosomal inactivation.
2019 accomplishments
In 2019, MTEM presented final results of the Phase 1/1b monotherapy study in lymphoma patients and initiated three Phase 2 studies in diffuse large B-cell lymphoma (DLBCL); a monotherapy study that has the potential to be pivotal and two combination studies, one with lenalidomide and the other with gemcitabine/oxaliplatin (GemOx).
The final Phase 1/1b results presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting included safety data on doses from 5-100 μg/kg, and efficacy data on 13 serum rituximab negative (RTX-neg) DLBCL or mixed DLBCL/FL subjects of whom 5 responded (38% objective response rate) across the range of 5 to 50 μg/kg doses. Of the 5 responses, 2 were complete responses (CRs) and 3 were partial responses (PRs). Three patients had stable disease (including 2 patients with 49% and 47% tumor reductions) and 5 patients had progressive disease. Of the 5 serum RTX-neg subjects with DLBCL who received MT-3724 at 50 μg/kg, the maximum tolerated dose (MTD), 3 responded (2 CRs, 1 PR).
The combination study with lenalidomide has demonstrated preliminary evidence of tolerability and efficacy with lenalidomide at standard doses and MT-3724 at 10 μg/kg. MT-3724 dosing at 25 μg/kg with lenalidomide is ongoing.
The combination study with GemOx has demonstrated preliminary evidence of efficacy but grade 2 innate immune adverse effects were seen with standard doses of gemcitabine and oxaliplatin and 10 μg/kg doses of MT-3724. The study protocol has been amended to include a revised schedule where MT-3724 dosing is initially sequenced with GemOx dosing.
Status updates and expected 2020 milestones
The potentially pivotal Phase 2 monotherapy DLBCL study is ongoing and is planned to enroll up to 100 patients. MTEM expects to announce updates on interim clinical results from this study and the ongoing lenalidomide and GemOx combination studies throughout 2020.
MT-5111 (HER2 ETB)

Candidate description
MT-5111 is a 2nd generation ETB technology that utilizes a genetically engineered de-immunized Shiga-like toxin A-subunit (SLTA) to reduce the potential for innate and adaptive immunogenicity. MT-5111 directly kills HER2-positive cells via ribosomal inactivation, a mechanism wholly distinct from approved HER2 targeted agents.
MT-5111 binds HER2 in the presence of trastuzumab and pertuzumab, creating the possibility of combining MT-5111 with other HER2 antibody-based agents.
MT-5111 is 55 kDa, almost a third smaller than traditional antibody and antibody drug conjugate (ADC) therapies, and, because of its smaller size, may have superior tumor penetration.
2019 accomplishments
In 2019, the IND for MT-5111 was accepted by the FDA and MTEM initiated a Phase 1 study, for which dosing began in 4Q19. MTEM also presented preclinical data on MT-5111 at the San Antonio Breast Cancer Symposium (SABCS).
Status update and expected 2020 milestones
The Phase 1 study is ongoing with multiple sites open for enrollment. MTEM expects to announce interim clinical results from this study in 2Q20 and additional data from the dose escalation portion of the study in 4Q20.
TAK-169 (CD38 ETB)

Candidate description
TAK-169 is a 2nd generation ETB that utilizes a genetically engineered de-immunized Shiga-like toxin A-subunit (SLTA) to reduce the potential for innate and adaptive immunogenicity. TAK-169 targets CD38, a poorly internalizing receptor expressed on myeloma cells, and directly kills CD38-expressing tumor cells via ribosomal inactivation.
Data in non-human primates suggest that TAK-169 can be dosed at higher doses than MT-3724 with a markedly reduced propensity of innate immune response compared with MT-3724.
Preclinical data suggest that TAK-169 retains activity in the presence of daratumumab, an approved CD38 antibody.
2019 accomplishments
In 2019, MTEM and partner Takeda presented preclinical data on TAK-169 at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, the IND for TAK-169 was accepted by the FDA, and Takeda initiated a Phase 1 study in relapsed/refractory multiple myeloma in 4Q19. In December 2019, TAK-169 received Orphan Drug Designation from the FDA.
Status update
Multiple sites are open for enrollment.
MT-6402 (PD-L1 ETB)

Candidate description
MT-6402 is a 3rd generation ETB that targets PD-L1, a poorly internalizing receptor expressed on various solid tumors. MT-6402 shares the de-immunized scaffold used with 2nd-generation ETBs and is further engineered to deliver a viral foreign class I peptide (antigen seeding) to alter the tumor immunophenotype.
MT-6402 utilizes Antigen Seeding Technology to deliver a foreign class I antigen derived from cytomegalovirus (CMV) inside the tumor for presentation on the tumor cell surface in complex with MHC class I molecules. MTEM has shown that antigen seeding allows CMV-reactive T-cells to recognize and destroy tumor cells. This T-cell response provides a mechanism of cell kill that is complementary to the ribosomal inactivation caused by the SLTA.
2019 accomplishments
In 2019, MTEM presented preclinical data on its PD-L1 targeted ETBs at the AACR (Free AACR Whitepaper) and Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meetings demonstrating potent anti-tumor effects on PD-L1+ tumor cells, good safety and pronounced pharmacodynamic effects in non-human primates, and a unique ability to alter the immunophenotype of tumors cells through antigen seeding.
Status update and expected 2020 milestones
An IND is expected to be filed and the Phase 1 study for MT-6402 is expected to be initiated in 2H20.
Earlier stage pipeline

Status update and expected 2020 milestones
MTEM continues to work on discovery of new ETBs against targets including CTLA-4, SLAMF-7, and CD45.
In 2020, MTEM expects to present preclinical data on new targets and new ETBs at conferences.
Corporate and Business Development

2019 accomplishments
On November 18, 2019, MTEM and Vertex Pharmaceuticals announced a strategic research collaboration to discover and develop novel targeted conditioning regimens that may enhance the hematopoietic stem cell transplant process, including transplants conducted as part of treatment with ex vivo CRISPR/Cas9 gene editing therapies such as CTX001. Under the collaboration, MTEM will conduct research activities for the use of ETBs for up to two targets selected by Vertex. The initial research will be focused on discovering a novel conditioning regimen using MTEM’s ETB technology platform. In addition, Vertex has an option to select a second target as part of the collaboration. Vertex made an up-front payment of $38 million to MTEM, including an equity investment. MTEM is also eligible to receive future development, regulatory and sales milestones and option payments of up to $522 million (across two targets) and tiered royalty payments on future sales.
On November 21, 2019, MTEM announced the pricing of an underwritten equity offering, the net proceeds of which were approximately $53.3 million, after deducting underwriting discounts and commissions and other estimated offering expenses payable by MTEM.
Status update and expected 2020 milestones
MTEM has three ongoing collaborations: the co-development collaboration with Takeda for TAK-169, the multi-target collaboration with Takeda for the discovery and development of new ETBs against two undisclosed oncology targets, and the multi-target collaboration with Vertex for the discovery and development of new conditioning regimens. All three of these collaborations are expected to advance in 2020.