On November 8, 2021 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported recent business and pipeline updates, as well as third quarter 2021 financial results (Press release, Beam Therapeutics, NOV 8, 2021, View Source [SID1234594706]).

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As part of today’s update, Beam announced that its Investigational New Drug (IND) application for BEAM-101 for the treatment of sickle cell disease was cleared by the U.S. Food and Drug Administration (FDA). BEAM-101, the company’s lead ex vivo base editing product candidate, is a patient-specific, autologous hematopoietic investigational cell therapy which incorporates base edits that mimic single nucleotide polymorphisms seen in individuals with hereditary persistence of fetal hemoglobin (HPFH) to potentially alleviate the effects of mutations causing sickle cell disease or beta-thalassemia. This is the first open IND for base editing technology, a next-generation form of CRISPR capable of making single base changes without creating double strand breaks in the DNA. Beam is preparing to initiate a Phase 1/2 clinical trial designed to assess the safety and efficacy of BEAM-101 for the treatment of sickle cell disease, which Beam refers to as the BEACON-101 trial.

"We are thrilled to share that the FDA has cleared our first IND. BEAM-101 has the potential to offer a one-time treatment for patients with sickle cell disease, and this clearance enables the important transition from a preclinical to a clinical-stage company, bringing us closer to our ultimate goal of helping patients," said John Evans, chief executive officer of Beam. "As leaders in the field of base editing, this milestone underscores the expertise of our team and the significant potential of our technology. We are grateful to the team members who have dedicated countless hours to this effort, and we look forward to this program’s continued evaluation in the clinic. As we look toward 2022, we believe we are well-positioned both financially and organizationally to execute on our vision."

"In addition to the clearance of our IND for BEAM-101, we are pleased to announce that we have initiated IND-enabling studies for BEAM-102, our Makassar base editing approach for the treatment of sickle cell disease," said Giuseppe Ciaramella, Ph.D., president and chief scientific officer of Beam. "We have also made continued progress on BEAM-201, our multiplexed base editing approach for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic leukemia as well as continued advancement across our robust portfolio, as showcased by a number of recent and upcoming data presentations demonstrating our leadership in base editing as well as optimized delivery technologies for our programs. Importantly, we also expect to nominate our first development candidate for in vivo base editing in the liver using LNP delivery for the treatment of patients with glycogen storage disease type Ia (R83C mutation) by the end of the year. We’ve made extraordinary progress as a company this year and remain committed to advancing novel science so that we may reach as many patients as possible."

Upcoming Base Editing Data Presentations

Preclinical data highlighting potential of CAR T multiplex base editing approach targeting CD5 at 2021 SITC (Free SITC Whitepaper) Annual Meeting. At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting, Beam will present preclinical data from its multiplex edited allogeneic CAR T research targeting CD5-positive hematologic malignancies in a poster titled "CD5 knockout enhances the potency of multiplex base-edited allogeneic anti-CD5 CAR T-cell therapy for the treatment of T-cell malignancies."
Multiple abstracts accepted for presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper). At this year’s ASH (Free ASH Whitepaper) meeting, Beam will present preclinical data highlighting its base editing approach to address sickle cell disease, including new preclinical data for BEAM-102, and data highlighting Beam’s in vivo high-throughput lipid nanoparticle (LNP) screening approach to identify novel LNPs that can deliver base editors to tissues beyond the liver, such as hematopoietic stem cells. In addition, Beam will present an overview on the application of base editing for the treatment of beta-hemoglobinopathies and other genetic blood disorders during a scientific program session. Details of the presentations can be found here.
Recent Base Editing Progress & Data Updates

BEAM-102 IND-enabling studies initiated. Beam has initiated IND-enabling studies for BEAM-102 for the treatment of sickle cell disease. BEAM-102 aims to directly correct the causative mutation in sickle cell disease by recreating a naturally-occurring normal human hemoglobin variant, HbG Makassar.
Preclinical data highlighting base editing approach to address GSDIa presented at European Society of Gene & Cell Therapy. Beam recently presented preclinical data demonstrating the ability of its liver-targeted base editing approach to directly correct R83C, one of the primary disease-causing mutations of glycogen storage disease type Ia (GSDIa), and the elimination of the disease phenotype in a novel in vivo model.
Optimized LNP delivery approaches for in vivo base editing to the liver and other tissues presented at TIDES 2021. Beam announced new preclinical data highlighting advancements with its approach to developing novel LNP formulations for increased in vivo liver editing potency, with high levels of editing at what Beam believes could be a clinically-relevant dose level of 1.0 mg/kg. Beam remains on track to nominate its first Development Candidate for in vivo base editing using LNP delivery by the end of 2021. Also at TIDES, Beam reported an update on its proprietary approach to developing LNPs to deliver base editors to tissues beyond the liver, including hematopoietic stem and progenitor cells.
Preclinical data highlighting potential of base editors to target disease drivers of chronic hepatitis B infection presented at 2021 International HBV Meeting. Beam recently presented data demonstrating the potential of its cytosine base editors to reduce viral markers, including hepatitis B surface antigen (HBsAg) expression, and prevent viral rebound of hepatitis B virus (HBV) in in vitro models.
Business Highlights

Executed non-exclusive option and license agreement with Sana Biotechnology for Cas12b. Under the agreement, Beam granted Sana non-exclusive commercial rights to utilize its CRISPR Cas12b system with certain allogeneic T-cell and stem cell-derived programs. The agreement excludes any rights to base editing using Beam’s Cas12b system, which rights remain exclusively with Beam. Sana agreed to pay Beam an upfront payment of $50 million, and Beam may also receive certain target option exercise fees, certain milestone payments upon the achievement of certain development and commercial sale milestones, and certain royalties on net sales of royalty-bearing products by Sana.
Third Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $933.4 million as of September 30, 2021, compared to $299.7 million as of December 31, 2020.
Research & Development (R&D) Expenses: R&D expenses were $54.6 million for the third quarter of 2021, compared to $29.8 million for the third quarter of 2020.
General & Administrative (G&A) Expenses: G&A expenses were $15.8 million for the third quarter of 2021, compared to $7.5 million for the third quarter of 2020.
Net Loss: Net loss attributable to common stockholders was $28.1 million, or $0.42 per share, for the third quarter of 2021, compared to $34.5 million, or $0.69 per share, for the third quarter of 2020.
About Sickle Cell Disease and Beta-Thalassemia

Sickle cell disease, a severe inherited blood disease, is caused by a single point mutation, E6V, in the beta globin gene. This mutation causes the mutated form of sickle hemoglobin (HbS) to aggregate into long, rigid molecules that bend red blood cells into a sickle shape under conditions of low oxygen. Sickled cells obstruct blood vessels and die prematurely, ultimately resulting in anemia, severe pain (crises), infections, stroke, organ failure, and early death. Sickle cell disease is the most common inherited blood disorder in the United States, affecting an estimated 100,000 individuals, of which a significant proportion are of African-American descent. Beta-thalassemia is another inherited blood disorder characterized by severe anemia caused by reduced production of functional hemoglobin due to insufficient expression of the beta globin protein. Transfusion-dependent beta-thalassemia (TDBT) is the most severe form of this disease, often requiring multiple transfusions per year. Patients with TDBT suffer from failure to thrive, persistent infections, and life-threatening anemia.

About BEAM-101
BEAM-101 is a patient-specific, autologous hematopoietic cell therapy under investigation for the treatment of sickle cell disease. BEAM-101 incorporates ex vivo base edits that mimic single nucleotide polymorphisms seen in individuals with hereditary persistence of fetal hemoglobin (HPFH) to potentially alleviate the effects of mutations causing sickle cell disease or beta-thalassemia by increasing the levels of fetal hemoglobin (HbF).