On April 27, 2021 Arch Oncology, Inc., a clinical-stage immuno-oncology company focused on the discovery and development of anti-CD47 biologic therapies, reported that it has closed a $105 million Series C financing co-led by Eventide Asset Management, Cowen Healthcare Investments and current investor 3×5 Partners, who were joined by new investors Adage Capital Management, Point72 Asset Management, Avego Healthcare Capital, FMB Research and Broadfin Holdings (Press release, Arch Oncology, APR 27, 2021, View Source;utm_medium=rss&utm_campaign=arch-oncology-secures-105-million-series-c-financing [SID1234578553]). Arch Oncology’s existing investors, including Roche Venture Fund, RiverVest Venture Partners, and Lightchain, also participated in the round. In connection with the financing, Joy Ghosh, Ph.D., Senior Research Analyst at Eventide Asset Management, Eric Pham, Ph.D., Associate at Cowen Healthcare Investments, and Joe Biller, Managing Director at 3×5 Partners, will join the Company’s Board of Directors.

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"This financing enables the clinical progress of our differentiated anti-CD47 product candidate AO-176, currently in Phase 1/2 clinical trials for solid tumors, both as a monotherapy and in combination with paclitaxel, and multiple myeloma. Looking forward, we plan to expand the AO-176 clinical program to include a combination trial with pembrolizumab (KEYTRUDA) in solid tumors, and a combination trial with standard therapies in multiple myeloma. We will also explore other indications and combinations consistent with our novel mechanisms of action," said Laurence Blumberg, M.D., President and Chief Executive Officer of Arch Oncology. "The quality of our new and existing investors is a testament to this pipeline and our mission on behalf of patients with cancer who need better therapeutic options."

AO-176 is an anti-CD47 IgG2 antibody in Phase 1/2 clinical trials for the treatment of patients with select solid tumors and with hematologic malignancies, both as monotherapy and in combination with standard therapies. AO-176 works by blocking the "don’t eat me" signal enabled by CD47’s interaction with SIRPa and inducing phagocytosis. It has a unique combination of features, positioning it to improve upon the safety and efficacy profile among anti-CD47 antibody therapies including: lower binding to normal cells in general and negligible binding to red blood cells; enhanced binding to CD47 in acidic environments found in tumors; and induction of programmed and immunogenic cell death.

"Arch Oncology’s highly differentiated approach to the development of anti-CD47 agents is a promising development in the immuno-oncology space," said John McKearn, Ph.D., Managing Director, RiverVest Venture Partners and Chairman of the Board of Arch Oncology. "We look forward to continuing to support the Company as it develops and advances its robust pipeline of promising drug candidates, including a broad clinical program for AO-176."

On April 27, 2021 SQZ Biotechnologies (NYSE: SQZ), a cell therapy company developing novel treatments for multiple therapeutic areas,reported that it will present new data on the company’s scaled cGMP cell therapy manufacturing program at the 2021 American Society for Gene and Cell Therapy Virtual Annual Meeting (ASGCT) (Free ASGCT Whitepaper) from May 11-14 (Press release, SQZ Biotech, APR 27, 2021, View Source [SID1234578585]). The company will also present findings on the performance advantages of cells engineered through its proprietary Cell Squeeze Technology.

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"There is tremendous therapeutic need for faster and more efficient delivery of impactful cell therapies to patients around the world," said Armon Sharei, PhD, Chief Executive Officer at SQZ Biotechnologies. "Through our manufacturing and therapeutic development programs, we strive to transform the current cell therapy paradigm and are excited to share our progress at ASGCT (Free ASGCT Whitepaper)."

Rapid, Scaled cGMP and Aseptic Manufacturing Program Data

Company scientists will present new data on its proprietary Cell Squeeze manufacturing technology demonstrating its ability to rapidly and reproducibly deliver cell therapy doses at scale. The presentation will show that the company’s cGMP and aseptic manufacturing program can process 10 billion cells per minute with greater than 90 percent cell viability. The company is delivering its first investigational drug (SQZ-PBMC-HPV) utilizing this core technology for its Phase 1 clinical trial in patients with Human Papillomavirus positive (HPV+) tumors.

"The company’s cell therapy manufacturing program has proven in our Phase 1 trial its ability to deliver reproducible investigational drug batches rapidly and at scale," said Howard Bernstein, MD, PhD, Chief Scientific Officer at SQZ Biotechnologies. "Our advances in cell therapy manufacturing will potentially enable multiple therapeutics across oncology, infectious disease, and immune disorders to be developed and delivered to a broad patient population."

Cell Performance Advantages

Additionally, in a poster presentation, company scientists assessed the use of Cell Squeeze technology to deliver pre-complexed CRISPR/Cas9 RNPs to achieve multiplex-edited primary human T cells. When comparing the functional effects of the Cell Squeeze technology to the commonly used electroporation approach, the authors found significant differences in transcriptional changes between the two treatments. Cells treated with electroporation corresponded with aberrant cytokine production, potentially resulting in premature T cell exhaustion. SQZ treated T cells, however, did not have disrupted transcriptional profiles or cytokine production and readily expanded post treatment with robustness similar to untreated cells.

"This work highlights the advantages of using the Cell Squeeze technology for cell engineering," said Jonathan Gilbert, PhD, Vice President of Exploratory Research at SQZ Biotechnologies. "We demonstrate preclinically a clear distinction in cell performance with the ability to achieve multiple, distinct gene edits with more viable and functional cells."

On April 27, 2021 Poseida Therapeutics, Inc. (NASDAQ: PSTX), a clinical-stage biopharmaceutical company utilizing proprietary genetic engineering platform technologies to create cell and gene therapeutics with the capacity to cure, reported three data presentations to be delivered at the upcoming American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 24th Annual Meeting, being held virtually May 11-14, 2021 (Press release, Poseida Therapeutics, APR 27, 2021, View Source [SID1234578669]).

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Poseida will present the following research at the 2021 ASGCT (Free ASGCT Whitepaper) Annual Meeting:

Oral Presentation
Title: Preclinical Evaluation of Combined Adeno-Associated Virus and Nanoparticle Delivery of piggyBac Transposon System for Durable Transgene Expression in the Growing Neonatal Murine Liver
Session Date/Time: Tuesday, May 11, 2021, 5:45pm – 6:00pm ET
Abstract Number: 30

Poster Presentations
Title: P-BCMA-ALLO1 — A Fully Allogeneic Stem Cell Memory T Cell (TSCM) CAR-T Therapy Targeting BCMA for the Treatment of Multiple Myeloma Shows Potent Anti-Tumor Activity
Session Date/Time: Tuesday, May 11, 2021, 8:00am – 10:00am ET
Abstract Number: 789

Title: Anti-c-kit CAR-T Cells Afford Effective Eradication of Human AML and Normal Hematopoietic Cells in a Preclinical Model of Safer Non-Genotoxic Stem Cell Transplant Conditioning
Session Date/Time: Tuesday, May 11, 2021, 8:00am – 10:00am ET
Abstract Number: 715

On April 27, 2021 Pyxis Oncology ("Pyxis" or the "Company") reported the targets of its three antibody-drug conjugate (ADC) candidates along with additional details and preclinical data supporting the potential of its ADC platform (Press release, Pyxis Oncology, APR 27, 2021, View Source [SID1234578535]). The Company will host a webcast with KOLs to further discuss the potential of Pyxis’ ADCs to improve the lives of patients with difficult-to-treat cancers.

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"ADCs represent a promising therapeutic modality, but historically their advancement has been limited due to on and off-target toxicities," said Ronald Herbst, Ph.D., Chief Scientific Officer of Pyxis. "Our ADC assets have been specifically designed and developed using site-specific conjugation chemistry to combine new and established targets, linkers and payloads. All three candidates are potent with highly stable linker-payload conjugation – characteristics that have led to superior therapeutic indexes. We believe our ADCs may apply to a broad patient population as single agents and in combination with immunotherapies to further improve the outcome for patients with difficult-to-treat cancers."

ADC candidate highlights:

PYX-201 is a first-in-class non-internalizing ADC that targets extra domain-B (EDB) of fibronectin. EDB is an oncofetal splice variant of fibronectin, a key component of the tumor extracellular matrix that is highly expressed across several solid tumors, including non-small cell lung cancer, ovarian, breast and pancreatic cancers. PYX-201 is designed to release an auristatin payload with bystander activity into the extracellular space to induce immunogenic cell death to kill tumor cells and their supporting infrastructure.

PYX-202 is a first-in-class internalizing ADC targeting delta-like 1 homolog (DLK-1), a tumor antigen that is restricted in normal tissues but expressed in a range of solid tumors, including small cell lung cancer, soft tissue sarcoma, hepatocellular carcinoma and neuroblastoma. PYX-202 utilizes a well-understood toxic agent, monomethyl auristatin payload (MMAE) and a beta-glucuronide cleavable linker designed to increase stability in circulation and reduce off-target toxicities.

PYX-203 is a best-in-class internalizing ADC targeting CD123, a clinically validated target primarily expressed in several high need hematologic malignancies, including acute myeloid leukemia (AML), myelodysplastic syndromes and others. PYX-203 utilizes a lysosomal cleavable linker and a highly potent cyclopropylpyrroloindole (CPI) DNA-damaging payload that may reduce the drug concentration needed to achieve positive treatment outcomes while limiting unwanted side effects. A larger patient population may benefit from PYX-203, including patients who otherwise would not respond to the standard of care.
Lara Sullivan, M.D., Chief Executive Officer of Pyxis, added, "We believe that our ADCs have the potential to overcome the challenges of difficult-to-treat cancers and help patients in need who currently do not respond to standard of care. Our expert team has incorporated a comprehensive understanding of ADC chemistry and cancer biology to identify the most promising therapeutic candidates that we expect will demonstrate improved activity, potency and stability. We look forward to progressing our ADC candidates to IND submissions next year."

Pyxis Oncology Webcast:

Title: Next-Generation ADCs: A Conversation With Key Opinion Leaders
Date: April 27, 2021
Time: 1:00 – 2:00 pm ET
Presenters:

Jeremy Barton, M.D., strategic oncology drug development consultant
Rakesh Dixit, Ph.D., DABT, President and Chief Executive Officer of Bionavigen
To register, click here. A replay of the event will be available here.

About PYX-201
PYX-201 is a first-in-class non-internalizing ADC that uniquely targets the oncofetal EDB isoform of fibronectin, a key component of the tumor extracellular matrix. As a non-internalizing ADC, PYX-201 binds to EDB and releases auristatin, a potent toxin, into the extracellular space after its linker is cleaved by cathepsin B to effectively kill tumor and tumor-associated cells. Through its unique mechanism of action, PYX-201 has significant potential as a single agent and in combination with immuno-oncology agents.

About PYX-202
PYX-202 is a first-in-class ADC targeting DLK-1, a tumor antigen that is restricted in normal tissues but expressed in a range of solid tumors. PYX-202 is designed to reduce toxicity by using a highly selective linker and a well-understood toxic agent, MMAE. PYX-202 uses a potent monoclonal antibody that has high affinity for DLK-1 and that drives efficient internalization of the ADC into tumor cells. PYX-202 utilizes a cleavable beta-glucuronide linker designed to increase stability in circulation. The linker is cleaved by an enzyme that is often overexpressed in a range of solid tumors, allowing for an added level of specificity that may further limit potential off-target activity. PYX-202 has significant potential as a monotherapy in tumors expressing high levels of DLK-1 and as a combination therapy with immunotherapies.

About PYX-203
PYX-203 is an ADC targeting CD123, an antigen primarily expressed in several high need hematologic malignancies and a clinically validated target being studied across multiple therapeutic modalities. Previous studies have found that CD123 is expressed on leukemic blasts as well as on AML stem cells, a critical population of cancer cells linked to disease relapse. Clinical evidence has found that CD123 expression is associated with poor outcomes, further supporting its potential role in disease progression. PYX-203’s DNA-damaging toxin, CPI, is a key component of the ADC, since its potency and specificity may lead to greater efficacy while limiting unwanted side effects even in patients who do not respond to standard of care.

On April 27, 2021 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the first quarter ended March 31, 2021 (Press release, CRISPR Therapeutics, APR 27, 2021, View Source [SID1234578554]).

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"We continue to make progress across our hemoglobinopathies and immuno-oncology programs on the clinical front, and expect to disclose data on multiple programs in 2021," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "Our revised agreement with Vertex for CTX001 streamlines operations and allows us to further invest in innovation to build upon the remarkable results we have seen with the program thus far. In addition, we are continuing to execute on our earlier stage pipeline and look forward to bringing our regenerative medicine and in vivo programs to the clinic."

Recent Highlights and Outlook

Beta Thalassemia and Sickle Cell Disease

The European Medicines Agency granted Priority Medicines (PRIME) designation to CTX001, an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy for the treatment of transfusion-dependent beta thalassemia (TDT). CTX001 was previously granted PRIME designation for the treatment of sickle cell disease (SCD) in 2020.
Enrollment and dosing are ongoing in the clinical trials for CTX001. More than 30 patients have been dosed with CTX001 across both trials to date. Completion of enrollment in both trials is expected in 2021.
Immuno-Oncology

The Company expects to report additional data in 2021 from its ongoing Phase 1 CARBON trial assessing the safety and efficacy of several dose levels of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19, for the treatment of relapsed or refractory B-cell malignancies.
CRISPR Therapeutics’ Phase 1 clinical trial assessing the safety and efficacy of several dose levels of CTX120, its wholly-owned allogeneic CAR-T investigational therapy targeting B-cell maturation antigen for the treatment of relapsed or refractory multiple myeloma, is ongoing. The Company expects to report top-line data from this trial in 2021.
CRISPR Therapeutics’ two independent Phase 1 clinical trials assessing the safety and efficacy of several dose levels of CTX130, its wholly-owned allogeneic CAR-T investigational therapy targeting CD70, for the treatment of both solid tumors and certain hematologic malignancies, are ongoing. The Company expects to report top-line data from these trials in 2021. Earlier this month, the Company announced preclinical data from its CAR-T program at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021. The data, presented in an e-poster session entitled, "CD70 knockout: A novel approach to augment CAR-T cell function, found that the generation of CAR-T cells including knockout of the CD70 show improved properties, including potency and persistence over CAR-T cells where the CD70 gene remains intact."
Regenerative Medicine

CRISPR Therapeutics and its partner ViaCyte remain on track to initiate a Phase 1/2 trial of their allogeneic stem cell-derived therapy for the treatment of Type 1 diabetes in 2021. The combination of ViaCyte’s stem cell capabilities and CRISPR’s gene editing capabilities has the potential to enable a beta-cell replacement product that may deliver durable benefit to patients without requiring immune suppression.
Other Corporate Matters

Earlier this month, CRISPR Therapeutics and its partner Vertex announced that the companies have amended their collaboration agreement to develop, manufacture and commercialize CTX001. Under the terms of the amended agreement, CRISPR Therapeutics will be responsible for 40% of the program costs and will receive 40% of the profits from future sales of CTX001 worldwide. With this revised agreement, Vertex will deploy the breadth of its established global capabilities and proven experience in development, manufacturing, and commercialization to maximize the potential for CTX001 to transform the lives of tens of thousands of patients in the U.S., Europe and other countries. CRISPR Therapeutics will continue to support the development of CTX001 and invest in further innovation to maximize its potential. The transaction is subject to customary closing conditions and clearances, including clearance under the Hart-Scott Rodino Antitrust Improvements Act.
First Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1,806.2 million as of March 31, 2021, compared to $1,690.3 million as of December 31, 2020. The increase in cash of $115.9 million was primarily driven by cash from financing activities of $226.0 million, which consists primarily of proceeds received from sales under our "at-the-market" offering in January and early February of 2021 offset by continuing operating expenses.

Revenue: Total collaboration revenue was $0.2 million for the first quarter of 2021 compared to $0.2 million for first quarter of 2020. Collaboration revenue primarily consisted of charges to partners for research activities.

R&D Expenses: R&D expenses were $90.6 million for the first quarter of 2021 compared to $54.2 million for the first quarter of 2020. The increase in expense was driven by development activities supporting the advancement of the hemoglobinopathies program and wholly-owned immuno-oncology programs, as well as increased headcount and supporting facilities related expenses.

G&A Expenses: General and administrative expenses were $24.5 million for the first quarter of 2021 compared to $19.6 million for the first quarter of 2020. The increase in general and administrative expenses for the year was primarily driven by headcount-related expense.

Net Income/Loss: Net loss was $113.2 million for the first quarter of 2021 compared to a net loss of $69.7 million for the first quarter of 2020.
About CTX001
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission for both TDT and SCD, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA) for SCD and TDT.

About the CRISPR-Vertex Collaboration
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development and commercialization of CTX001 and split program costs and profits worldwide 60/40 with CRISPR Therapeutics. This amendment is subject to customary closing conditions and clearances, including clearance under the Hart-Scott Rodino Antitrust Improvements Act.

About CLIMB-Thal-111
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-SCD-121
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CTX110
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial.

About CARBON
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.

About CTX120
CTX120, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting B-cell maturation antigen, or BCMA. CTX120 is being investigated in an ongoing Phase 1 single-arm, multi-center, open-label clinical trial designed to assess the safety and efficacy of several dose levels of CTX120 for the treatment of relapsed or refractory multiple myeloma. CTX120 has been granted Orphan Drug designation from the FDA.

About CTX130
CTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of both solid tumors, such as renal cell carcinoma, and T-cell and B-cell hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1, single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively.