On January 11, 2021 Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported an update on its ongoing APVO436 phase 1 clinical trial (Press release, Aptevo Therapeutics, JAN 11, 2021, View Source [SID1234573836]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company noted that patient dosing in cohorts 1 through 8 has been completed and enrollment in cohort 9 has commenced. A total of 36 patients have been enrolled and treated with APVO436 to date. No evidence of dose-limiting toxicities (DLTs) was observed in cohorts 5-8.

"2020 was a very busy and exciting year at Aptevo, with progress on many fronts. Notably, two patients in cohort 6 of our APVO436 Phase 1a clinical trial achieved complete remission. This development greatly encouraged our research partners and our inhouse teams, who have poured their passion and energy into this trial," said Mr. Marvin White, President and CEO of Aptevo Therapeutics.

"In 2021, we look forward to advancing our APVO436 clinical trial and improving patient outcomes, while recognizing that each patient is unique. Our first patient in cohort 6 who had complete remission continues therapy, while the second patient in cohort 6 who also had complete remission progressed and discontinued therapy. Importantly, we are now in a critical phase of the study, within the therapeutic range,"

"We believe that the work we are doing is meaningful and important, and we will continue to focus on developing candidates that target cancers, ultimately increasing a patients’ chance of survival. We have multiple candidates moving towards clinical development, and our ADAPTIR and ADAPTIR-FLEX technology platforms are uniquely positioned to develop and advance our studies," concluded Mr. White.

About APVO436

APVO436 is an optimized bispecific antibody candidate designed to simultaneously target CD123 and CD3 and redirect T-cell cytotoxicity to the tumor. It is currently being evaluated in a Phase 1/1b open-label, dose-escalation study evaluating the safety and pharmacokinetic profile. APVO436 was built on Aptevo’s proprietary ADAPTIR protein therapeutic platform. Focused on generating novel, targeted bispecific antibody-based immunotherapies for cancer the ADAPTIR platform offers key advantages over other bispecific formats, derived in part from the flexible and modular nature of the ADAPTIR structure. These advantages include: (i) achieving potent biological activity and extended half-life while retaining desirable manufacturing characteristics and (ii) unique properties for redirecting T-cell cytotoxicity (RTCC) compared to other bispecific platforms, including a favorable cytokine release profile.

On January 11, 2021 Blueprint Medicines Corporation (NASDAQ: BPMC) reported an update on key portfolio milestones and outlined a strategic roadmap to become the world’s leading precision therapy company (Press release, Blueprint Medicines, JAN 11, 2021, View Source [SID1234573835]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"For the first time, we enter a new year as a fully integrated, global biopharmaceutical company, with four regulatory approvals in the United States and Europe in 2020, a pipeline of eight wholly owned or partnered precision therapies, and the strongest financial position since our inception," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "With this solid foundation, we are now scaling our ambition and aim to make real the promise of precision medicine to improve and extend life for as many people with cancer and hematologic disorders as possible. We will do this by bringing our medicines to more patients globally, rapidly advancing a wave of new therapeutic candidates to clinical proof-of-concept, and further expanding our platform-enabled research pipeline."

In addition, Blueprint Medicines reported the achievement of several portfolio milestones:

AYVAKIT received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe indolent systemic mastocytosis (SM), which encompasses the majority of patients with SM, highlighting the medical need in this population as well as the clinical potential of AYVAKIT to demonstrate substantial improvement over the current standard of care.
Positive top-line results from a Phase 1 trial in healthy volunteers showed BLU-263 was well-tolerated across a range of single- and multiple-ascending doses predicted to potently inhibit D816V mutant KIT, the underlying SM disease driver. These data support development of BLU-263 as a potential treatment for patients with SM and other mast cell disorders.
The company nominated a selective, brain-penetrant development candidate for treatment-resistant double-mutant EGFR-driven non-small cell lung cancer (NSCLC), with the potential to be first-in-class, showing potent activity against the activating L858R or exon 19 deletion mutations and the acquired C797S mutation, the most common on-target resistance mutation to osimertinib.
The company nominated a development candidate targeting MAP4K1, a kinase believed to play a role in T-cell regulation, with the potential to be best-in-class. The program was developed under the company’s cancer immunotherapy collaboration with Roche. In addition, Blueprint Medicines and Roche have amended their agreement to focus on MAP4K1 and one additional undisclosed target, collectively identified as the most promising targets of the collaboration to date.
Entering 2021, the company’s key strategies and goals include:

1. Accelerate global adoption of AYVAKIT and GAVRETO (pralsetinib)

AYVAKIT, a selective KIT and PDGFRA inhibitor, is approved in the U.S. and Europe for the treatment of patients with unresectable or metastatic gastrointestinal stromal tumor driven by certain PDGFRA mutations.

Obtain FDA approval and launch AYVAKIT in advanced SM in the U.S. in the second half of 2021.
Submit a Type II variation marketing authorization application (MAA) to the European Medicines Agency (EMA) for AYVAKYT (avapritinib) for advanced SM in the first quarter of 2021.
Present registrational data from the PATHFINDER trial of AYVAKIT in advanced SM in the first half of 2021.
Complete enrollment of the registration-enabling Part 2 of the PIONEER trial of AYVAKIT in non-advanced SM in mid-2021.
GAVRETO, a selective RET inhibitor, is approved in the U.S. for the treatment of patients with certain advanced or metastatic RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancer. Under a global collaboration, Blueprint Medicines and Roche are developing and commercializing GAVRETO for the treatment of RET-altered cancers.

Obtain regulatory approval from the European Commission and launch GAVRETO in RET fusion-positive NSCLC in Europe in the first half of 2021.
Submit a Type II variation MAA to the EMA for GAVRETO for RET-altered thyroid cancers in the second half of 2021.
Initiate a GAVRETO cohort in Roche’s TAPISTRY tumor-agnostic platform trial in the second half of 2021.
Submit marketing applications for GAVRETO for RET-altered NSCLC and thyroid cancers across multiple additional global geographies in 2021.
2. Advance a new wave of innovative therapeutic candidates into clinical development, with plans to achieve rapid proof-of-concept and regulatory approval.

BLU-263, a next-generation selective KIT inhibitor

Initiate the Phase 2 HARBOR trial of BLU-263 in patients with non-advanced SM in mid-2021.
Development candidates for treatment-resistant EGFR-driven NSCLC

Initiate a Phase 1 trial of BLU-945, a triple-mutant EGFR inhibitor, in patients with treatment-resistant EGFR-driven NSCLC in the first half of 2021.
Initiate a Phase 1 trial of the company’s double-mutant EGFR inhibitor in patients with treatment-resistant EGFR-driven NSCLC by the end of 2021.
Present foundational preclinical data for the company’s double-mutant EGFR inhibitor in the first half of 2021.
Present preclinical data supporting combination of the company’s wholly owned double- and triple-mutant EGFR inhibitors in treatment-naïve EGFR-driven NSCLC in the second half of 2021.
Development candidate targeting MAP4K1, under the cancer immunotherapy collaboration with Roche

Present foundational preclinical data in the first half of 2021.
3. Further expand the company’s precision medicine pipeline with a focus on delivering transformational benefit to patients with cancer and hematologic disorders.

Expand pipeline with one or more development candidates in 2021.
Pursue external opportunities to complement the company’s precision medicine pipeline.
Financial Guidance

Based on its current operating plans, Blueprint Medicines continues to anticipate its existing cash, cash equivalents and investments, together with anticipated future product revenues, will provide sufficient capital to enable the company to achieve a self-sustainable financial profile.

On January 11, 2021 Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative medicines based on cancer cell biology, reported a business update reviewing 2020 achievements and outlining the Company’s key business objectives for 2021 (Press release, Cyclacel, JAN 11, 2021, View Source [SID1234573834]). The Company will present at Biotech Showcase Digital 2021 taking place virtually from January 11 to 15 with a prerecorded session of the company presentation. Spiro Rombotis, President & Chief Executive Officer, will provide an overview of the Company and progress in key programs. Cyclacel will host one-on-one meetings with investors and industry stakeholders during the event. Registered Biotech Showcase Digital 2021 attendees may request one-on-one meetings with Cyclacel through the partneringONE system.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"With the recent appointment of Dr. Mark Kirschbaum as our CMO and the December 2020 strategic investment from Acorn Bioventures, we are well resourced to progress fadraciclib and CYC140, our two internally discovered molecules," said Spiro Rombotis, President and Chief Executive Officer. "Fadraciclib, a CDK2/9 inhibitor, has shown promising clinical activity and tolerability in patients with advanced cancers and CYC140, a PLK1 inhibitor, is in a first-in-human study. As the next step in our clinical development program we will evaluate both agents, dosed orally, across a broad spectrum of solid tumors and hematological malignancies as part of our strategy of identifying clinical activity which may lead to registration-enabling studies."

2020 Key Achievements

Data from Phase 1 study of fadraciclib as a single agent reported at the Plenary Session of the 32nd EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium
• Radiographically confirmed partial response (PR) after a month and a half on i.v. fadraciclib: MCL1-amplified endometrial cancer; failed seven lines of prior therapy; continuing treatment for more than 16 months with 96% reduction in target tumor lesions
• High bioequivalence observed in 5 patients treated with oral fadraciclib
Enrolled 19 patients evaluating i.v. fadraciclib in combination with venetoclax in patients with relapsed or refractory AML/MDS and CLL with evidence of antileukemic activity
Enrolled five patients evaluating i.v. CYC140 in patients with advanced leukemias
Enrolled 12 patients in Phase 1/2 study evaluating an oral regimen of sapacitabine in combination with venetoclax in patients with relapsed or refractory AML/MDS
Announced peer-reviewed publication of a fadraciclib review in PLOS ONE. Authored by scientists from Cyclacel and The Institute of Cancer Research, London, the publication describes the discovery of fadraciclib and shows that its targeting of CDK2 and CDK9 leads to broad therapeutic potential
Appointed Mark Kirschbaum, M.D. as Senior Vice President and Chief Medical Officer. Dr. Kirschbaum is a highly experienced hematologist/oncologist with over 30 years of experience in molecular medicine, new drug development, clinical trial design and patient care
Appointed Brian Schwartz, M.D, formerly CMO at ArQule, Inc., and Karin L. Walker, Chief Accounting Officer of Prothena Corporation plc, to the Board of Directors
Raised approximately $30 million in net cash in two equity financings and related warrant exercises providing estimated capital to early 2023
In 2021, Cyclacel will commence streamlined Phase 1/2 clinical studies, initially of oral fadraciclib and subsequently of oral CYC140, in a broad range of solid tumors and hematological malignancies. These studies are supported by fadraciclib’s Phase 1 clinical data and its transcriptional mechanism of action enabling apoptosis of cancer cells and the extensive preclinical data of CYC140 demonstrating its antimitotic mechanism and broad therapeutic potential in several solid tumors and hematological malignancies.

The clinical development plan for these studies calls for parallel evaluation of different schedules of the two agents in multiple cohorts defined by cancer histology and collection of biospecimens for translational analysis. The aim of these studies is to identify clinical activity which may lead to registration-enabling studies.

Key Business Objectives for 2021

First patient dosed with oral fadraciclib in Phase 1/2 advanced solid tumor study
First patient dosed with oral CYC140 in Phase 1/2 advanced solid tumor study
Manufacture clinical supplies of fadraciclib and CYC140 for registration-enabling studies
Data on safety and antileukemic activity from the i.v. fadraciclib-venetoclax Phase 1 study in relapsed/refractory AML and CLL
Data from the sapacitabine-venetoclax Phase 1/2 study in relapsed/refractory AML or MDS
Initial data from the CYC140 Phase 1 First-in-Human study in patients with advanced leukemias
Data from the Phase 1b/2 IST of sapacitabine-olaparib combination in patients with BRCA mutant metastatic breast cancer when reported by the investigators

On January 11, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported 2021 milestone targets for its pipeline of four drug candidates, including data updates from multiple clinical studies and the initiation of new clinical studies (Press release, Turning Point Therapeutics, JAN 11, 2021, View Source [SID1234573833]). The company also updated its cash position as of Dec. 31, 2020.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Following a pivotal year in 2020, we believe we have even greater opportunities in 2021 to further advance our pipeline by potentially modifying our SHIELD-1 study to a registrational Phase 1/2 design, adding three new clinical trials, including two anticipated combination studies and a Phase 1 study of our fourth drug candidate, our novel ALK-inhibitor TPX-0131, and reporting initial or updated data from our three clinical stage drug candidates," said Athena Countouriotis, M.D., president and chief executive officer. "At the same time, we have continued to invest in our discovery engine and look forward to the second half of the year when we plan to outline our focus and goals to further expand the pipeline."

2020 Achievements and 2021 Milestone Targets

Repotrectinib, ROS1 and TRK Inhibitor

In 2020, repotrectinib was granted breakthrough-therapy designation (BTD) and received its second and third fast-track designations. In addition, the company signed an exclusive license agreement with Zai Lab to develop and commercialize repotrectinib in greater China and reported early interim data from the Phase 2 TRIDENT-1 registrational study.

2021 Milestone Targets:

Present updated data from the TRIDENT-1 study in TKI-naive patients with ROS1-positive advanced non-small cell lung cancer (NSCLC) in a mini-oral presentation on Jan. 31 at the World Conference on Lung Cancer

Provide an update on the overall Phase 2 TRIDENT-1 registrational study timeline in the first quarter

Initiate the Phase 2 TRIDENT-2 combination study in patients with KRAS mutant NSCLC mid-year

Provide clinical data updates from certain cohorts of the Phase 2 TRIDENT-1 study in the second half
TPX-0022, MET/SRC/CSF1R Inhibitor

In 2020, Turning Point advanced its clinical development of TPX-0022 and reported initial data from the Phase 1 SHIELD-1 study in an oral presentation during the plenary session at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) medical symposium.

Earlier today, the company announced the broadening of its collaboration with Zai Lab to include an exclusive licensing agreement for TPX-0022 in greater China.

2021 Milestone Targets:

Initiate the Phase 2 portion of SHIELD-1, pending FDA feedback, in the second half

Initiate the Phase 2 SHIELD-2 study of TPX-0022 in combination with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in the second half

Provide a clinical data update from the Phase 1 portion of the SHIELD-1 study in the second half
TPX-0046, RET Inhibitor

In 2020, Turning Point presented preclinical data highlighting the potent inhibition of TPX-0046 against wildtype RET and RET mutations, and continued its ongoing Phase 1 study of TPX-0046.

2021 Milestone Target:

Report early interim data from initial patients enrolled in the dose finding portion of the TPX-0046 Phase 1 study in the first half
TPX-0131, ALK Inhibitor

In 2020, Turning Point nominated TPX-0131 as its ALK inhibitor drug candidate, advanced its IND enabling studies, and presented preclinical data highlighting its ability to overcome ALK resistant mutations refractory to approved ALK inhibitors.

2021 Milestone Targets:

Submit the IND for TPX-0131 in the first quarter
Initiate a Phase 1 clinical study of TPX-0131 in the first half
Early Discovery Pipeline

In 2020, Turning Point named Siegfried Reich as chief scientific officer and made investments to advance its research strategy.

2021 Milestone Target:

Outline research strategy, focus and milestones for future development candidates in the second half
Financial

In 2020, Turning Point completed follow-on stock offerings generating gross proceeds of $374 million and $460 million. The company enters 2021 with approximately $1.1 billion in cash, cash equivalents and marketable securities as of Dec. 31, 2020, which is expected to fund operations into 2024.

On January 11, 2021 Strand Therapeutics, a privately held developer of next-generation, programmable mRNA therapeutics for cancer and other diseases, and BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160) reported that they have entered into an option and license agreement aimed at developing and commercializing Strand’s innovative, multi-functional mRNA treatments for solid tumors (Press release, Strand Therapeutics, JAN 11, 2021, View Source [SID1234573832]). BeiGene has secured an option to an exclusive license to develop and commercialize in Asia (excluding Japan), Australia, and New Zealand up to two immuno-oncology programs using Strand’s intratumoral or systemic delivery mechanism, which is designed to deliver a tumor microenvironment-modifying mRNA directly to the tumor site.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Strand has developed the first platform for the creation of programmable, long-acting mRNA therapeutics capable of delivering multi-functional treatments for deadly diseases, with an initial aim of developing potentially curative treatments for solid tumor cancers. The company’s self-replicating mRNAs are bioengineered to enable precise control of the location, timing, intensity, and duration of therapeutic protein expression for improved efficacy and lower toxicity.

"BeiGene is a recognized global leader in the development and commercialization of innovative, high-quality cancer therapeutics," said Jacob Becraft, Ph.D., Co-founder and Chief Executive Officer of Strand. "This collaboration between our two companies provides strong validation of Strand’s next-generation mRNA platform and our work to advance mRNA-based medicines beyond vaccines into potentially curative therapies."

"We look forward to working closely with BeiGene’s unsurpassed clinical team to accelerate the development of our solid tumor immuno-oncology therapies," said Tasuku Kitada, Ph.D., Co-founder, President, and Head of R&D of Strand. "The aim of both our companies is to increase patient access to cutting-edge therapeutics by providing safe and effective treatments that are more easily administered, cost-effective, and scalable."

"Strand’s programmable mRNA technology is incredibly exciting as a cutting-edge therapeutic platform and is expected to help us build novel mRNA-based immuno-oncology therapeutics for the treatment of cancer. We look forward to exploring this technology further and to collaborating with Strand as we advance up to two development programs with this new approach," said Lusong Luo, Ph.D., Senior Vice President of External Innovation at BeiGene.

Under the terms of the agreement, Strand will receive an upfront cash payment of $5 million and will also be eligible to receive additional near-term payments totaling up to $28 million, inclusive of BeiGene’s exercise of its options to the two programs following initial proof-of-concept studies. Additionally, Strand is eligible to receive payments from BeiGene based upon the achievement of certain development, regulatory, and sales milestones for a total deal value of up to $277 million, together with tiered royalties on any product sales in the licensed territory. In connection with the agreement, Strand also received investments of $10 million, including $5 million from BeiGene.