On November 7, 2022 Calidi Biotherapeutics, Inc. (Calidi), a clinical-stage biotechnology company that is pioneering allogeneic cell-based platforms to revolutionize oncolytic virus therapies, reported the presentation of new pre-clinical data from the company’s SuperNova-1 (SNV1) platform at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting, taking place in Boston, Massachusetts and virtually, November 8-12, 2022 (Press release, Calidi Biotherapeutics, NOV 7, 2022, View Source [SID1234623228]).

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!

SNV1 is composed of adipose tissue-derived allogeneic stem cells (AD-MSC) loaded with tumor-selective CAL1 oncolytic vaccinia virus that is designed to overcome multiple innate and adaptive immune barriers that restrict traditional oncolytic virotherapy. Early Calidi research has shown the potential ability of the SNV1 platform to shield the viral payload from the immune system, supporting efficient delivery to tumor sites and effectively potentiating oncolytic viruses’ therapeutic efficacy.

The poster presentation details the evaluation of SNV1 in multiple tumor-bearing mouse models, where SNV1 was tested for its ability to resist humoral immune-mediated inactivation in cell culture. Additionally, following either single or three dose regimens, tumor growth inhibition of multiple human xenografts and murine syngeneic models was examined. The study also investiagted the molecular signature associated with the infection of mesenchymal stem cells (MSC) with the oncolytic virus CAL1 by RNA sequencing.

"These incremental data validate our belief in the potential of SNV1 and the use of stem cells as a delivery and potentiation platform for oncolytic viruses," said Antonio F. Santidrian, Ph.D., SVP, Global Head of R&D of Calidi Biotherapeutics. "Through the demonstration of tumor growth inhibition across multiple pre-clinical models as well as the ability to overcome rapid inactivation by the immune system, we believe SNV1 can revolutionize the use of oncolytic virotherapy to treat a broad range of cancers and look forward to advancing this promising asset into the clinic."

Key highlights from the poster presentation are below:

The SNV1 stem cell-based platform protects and potentiates oncolytic vaccinia virus by circumventing humoral innate and adaptive immune barriers, resulting in enhanced anticancer effects in tumor-bearing mouse models.
SNV1 provided instantly active viral particles for immediate infection in the injected tumors, transforming the tumor environment from "cold" to "hot" locally and systemically, and leading to significant tumor growth inhibitions in multiple human and mouse tumor models.
Repeated intratumoral administrations of SNV1 inhibited treated as well as distant untreated tumors. These effects were also associated with a significant increase of tumor-infiltrating lymphocytes in both treated and untreated tumors.
RNA-sequenced genome-wide analysis provided insights into the valuable role of stem cells in the immunotherapeutic MOA of SNV1.

On November 7, 2022 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported financial results and business highlights for the third quarter ended September 30, 2022 and shared recent operational progress (Press release, bluebird bio, NOV 7, 2022, View Source [SID1234623227]).

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 third quarter officially launched bluebird bio as a commercial gene therapy company, following FDA approvals of ZYNTEGLO for beta-thalassemia and SKYSONA for cerebral adrenoleukodystrophy," said Andrew Obenshain, CEO bluebird bio. "Positive momentum continues to build through the ZYNTEGLO launch and we are on track to complete our first cell collection this quarter. Additionally, we are readying SKYSONA for commercial availability and are on track to file our biologics licensing application for lovo-cel for sickle cell disease in Q1 2023. As a result of milestones in the quarter, we are adjusting our fourth quarter 2022 financial guidance to account for post-marketing commitment expenses and increased investment in current and upcoming launches, which will enable the Company to fully benefit from its first-in-class position. Today, we are also very pleased to welcome Chris Krawtschuk as bluebird’s next chief financial officer. Chris brings significant experience leading and advising financial and capital strategies for a multitude of commercial organizations and will play a critical role in our financing strategy and the evolution of bluebird’s balance sheet as a commercial company."

RECENT HIGHLIGHTS

ZYNTEGLO FDA APPROVAL AND COMMERCIAL LAUNCH PROGRESS

On August 17, 2022, the U.S. Food and Drug Administration (FDA) approved ZYNTEGLO (betibeglogene autotemcel), the first one-time gene therapy custom-designed to treat the underlying genetic cause of beta‑thalassemia in adult and pediatric patients who require regular red blood cell (RBC) transfusions.
Following approval, the Company has made significant progress on its first US commercial launch and remains on track for first apheresis (cell collection) in the fourth quarter of this year. Two months post approval, 27 patients have initiated benefits verification and approximately one-third of those patients have progressed to prior authorization. While we anticipate that not all patients will proceed with treatment, these early indicators demonstrate significant demand across a rare disease population. Of note, the process to initiate gene therapy treatment once a patient and their provider have decided it is right for them may take several weeks as the patient completes the consent process, benefits verification and prior authorization.
bluebird has completed activation of all wave one qualified treatment centers (QTCs) and the Company’s QTC network is on track to reach low double digits by the end of the year, as previously guided. In addition to the Company’s planned list of QTCs, bluebird has received inbound requests for inclusion in its QTC network from more than 30 adult and pediatric institutions, demonstrating eagerness to treat. bluebird’s hemoglobinopathies QTC footprint is expected to scale to 40-50 centers by the end of 2023 and is designed to maximize the beta-thalassemia launch and prepare for the potential future launch of lovotibeglogene autotemcel (lovo-cel) for sickle cell disease (SCD), pending regulatory approval.
To date, the Company has signed outcomes-based agreements with pharmacy benefit managers (PBMs) representing more than 40 national and regional plans. Additionally, to date 12 payers have issued medical coverage policies that are favorably aligned to ZYNTEGLO’s clinical evidence base.
SKYSONA FDA APPROVAL AND COMMERCIAL LAUNCH PROGRESS

On September 16, 2022, the U.S. FDA granted Accelerated Approval for SKYSONA (elivaldogene autotemcel) to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD).
Concurrent with the FDA approval, the previous clinical hold on the eli-cel clinical development program was lifted.
Since approval, bluebird has activated three QTCs to treat patients with CALD. The Company anticipates commercial readiness for SKYSONA in the fourth quarter of 2022.
BETA-THALASSEMIA AND SICKLE CELL DISEASE DATA AT ASH (Free ASH Whitepaper) 2022

Updates on the Company’s beta-thalassemia and sickle cell disease clinical development programs will be presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 10-13, 2022 at the Ernest N. Morial Convention Center in New Orleans, Louisiana.

BETA-THALASSEMIA DATA
Poster (#2348): Long Term Outcomes of 63 Patients with Transfusion-Dependent β-Thalassemia (TDT) Followed Up to 7 Years Post-Treatment with betibeglogene autotemcel (beti-cel) Gene Therapy and Exploratory Analysis of Predictors of Successful Treatment Outcomes in Phase 3 Trials
Presenting Author: Mark C. Walters, MD, Medical Director, Jordan Family Center for BMT & Cellular Therapies Research, UCSF Benioff Children’s Hospital Oakland, Oakland, CA
Date/Time: Sunday, December 11, 2022, 6:00 PM – 8:00 PM
Poster (#3665): Long-Term Patient-Reported Outcomes Following Treatment with Betibeglogene Autotemcel in Patients with Transfusion-Dependent β-Thalassemia
Presenting Author: Professor Franco Locatelli, Director, Department of Pediatric Hematology and Oncology, Ospedale Pediatrico Bambino Gesù, Rome, Italy
Date/Time: Monday, December 12, 2022, 6:00 PM – 8:00 PM
SICKLE CELL DISEASE DATA
Oral Presentation (#11): lovo-cel (bb1111) Gene Therapy for Sickle Cell Disease: Updated Clinical Results and Investigations into Two Cases of Anemia from Group C of the Phase 1/2 HGB-206 Study
Presenting Author: Mark C. Walters, MD, Medical Director, Jordan Family Center for BMT & Cellular Therapies Research, UCSF Benioff Children’s Hospital Oakland, Oakland, CA
Date/Time: Saturday, December 10, 2022, 10:30 AM
Abstracts are now live on the ASH (Free ASH Whitepaper) website.

MANAGEMENT UPDATE

Effective today, following the filing of the Company’s 10-Q with the SEC, Chris Krawtschuk has been appointed Chief Financial Officer (CFO). Chris joins bluebird from Jubilant Pharma, a global integrated pharmaceutical company, where he was CFO. He brings over 25 years of experience in finance, accounting, tax, strategy, business development, and capital allocation for commercial execution. Prior to Jubilant, Chris was the CFO of MorphoSys US and VP Global Lead Business Unit Controller at Pfizer. Earlier in his career Chris spent 15 years at PwC, finishing his tenure as Managing Director in PwC’s Capital Markets and Accounting Advisory practice.

Interim CFO Katherine Breedis will continue to lead strategic finance initiatives for bluebird and partner with Chris through a transition period; thereafter, she will continue to serve as a strategic advisor.
NEW LABORATORY SPACE

bluebird reported that the Company has signed a 3-year sublease for 42,000 square feet of lab space located at 100 Hood Park Drive in Charlestown, MA, in close proximity to the Company’s Somerville corporate headquarters. bluebird expects to transition lab operations from its Cambridge location to Charlestown by mid-2023. The new lab space is expected to result in approximately $3 million in annual cost savings beginning in 2024.
UPCOMING ANTICIPATED MILESTONES

COMMERCIAL

ZYNTEGLO: Consistent with previous guidance, the Company anticipates the first commercial ZYNTEGLO infusion in Q1 2023. The Company will realize revenue upon infusion.
SKYSONA: bluebird anticipates commercial readiness for SKYSONA in the fourth quarter of 2022.
REGULATORY

LOVO-CEL: The Company expects to complete vector and drug product analytical comparability for the lovo-cel BLA in the fourth quarter of 2022 and remains on track to submit its BLA for lovo-cel in Q1 2023.
LOVO-CEL: The Company remains in active communication with the FDA to resolve the lovo-cel partial clinical hold and resume enrollment and treatment of patients under the age of 18.
THIRD QUARTER 2022 FINANCIAL RESULTS

Cash Position: The Company’s cash and cash equivalents and marketable securities balance was approximately $141 million as of September 30, 2022. In addition, the Company ended the quarter with $45 million in restricted cash. As a result of increased investment in current and upcoming launches, as well as post-marketing commitments related to the FDA approvals of ZYNTEGLO and SKYSONA, bluebird is adjusting its fourth quarter 2022 projected cash burn to between $75 million to $80 million. bluebird anticipates providing full year 2023 guidance early next year.

As of September 30, 2022, the Company has raised approximately $54.1 million in net proceeds through its At-the-Market (ATM) equity facility. Of this $54.1 million, $46.1 million in net proceeds were realized in the third quarter. The Company expects its cash, cash equivalents and marketable securities, together with the anticipated release of $40 million of the Company’s restricted cash in the fourth quarter of 2022, will be sufficient to meet bluebird’s planned operating expenses and capital expenditure requirements into the second quarter of 2023.

This quarter the Company received two Priority Review Vouchers (PRVs) following the FDA approvals of ZYNTEGLO and SKYSONA and is exploring options to monetize both PRVs. Concurrently, the Company is exploring additional financing opportunities, including public or private equity and debt financings.
Revenues: Total revenue was $0.1 million for the three months ended September 30, 2022, compared to $1.0 million for the three months ended September 30, 2021.
R&D Expenses: Research and development expenses from continuing operations were $53.1 million for the three months ended September 30, 2022, compared to $73.7 million for the three months ended September 30, 2021. The decrease of $20.6 million was primarily due to decreased employee compensation, benefits, other head-count related expenses, information technology and facility-related costs, clinical trial costs, and material production costs. These decreased costs were partially offset by increased platform costs.
SG&A Expenses: Selling, general and administrative expenses from continuing operations were $33.4 million for the three months ended September 30, 2022, compared to $42.2 million for the three months ended September 30, 2021. The decrease of $8.8 million was primarily due to decreased employee compensation, benefit, and other head-count related expenses and decreased commercial readiness activities due to the Company’s decision to focus its efforts on the U.S. market. These decreased costs were partially offset by increased information technology and facility-related costs, primarily attributed to rent expense due to the addition of the Company’s office leases in Cambridge and Somerville, Massachusetts. Cambridge rent expense was offset by $7.5 million in sublease rental income generated for the three months ended September 30, 2022, captured in "other income" on the Company’s income statement.
Net Loss: Net loss from continuing operations was $76.5 million for the three months ended September 30, 2022, compared to $216.8 million for the three months ended September 30, 2021.

On November 7, 2022 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 reported that it has entered into a definitive agreement with certain institutional investors for the issuance and sale of 800,000 shares of its common stock (or common stock equivalents) for a price of $2.50 per share, for gross proceeds of approximately $2.0 million, in a registered direct offering (Press release, Bio-Path Holdings, NOV 7, 2022, View Source [SID1234623225]). Additionally, in a concurrent private placement, Bio-Path has also agreed to issue to such investors unregistered warrants. The offerings are expected to close on or about November 9, 2022, subject to the satisfaction of customary closing conditions.

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!

Roth Capital Partners is acting as the sole placement agent for the offerings.

Bio-Path will issue to the investor in the concurrent private placement warrants to purchase up to 800,000 shares of common stock, which represents 100% of the number of shares of common stock (or common stock equivalents) issued in the registered direct offering, with an exercise price $2.85 per share and exercise period commencing six (6) months following the issuance date and a term of five and one-half (5.5) years.

Bio-Path currently intends to use the net proceeds from the offerings for working capital and general corporate purposes.

The shares of common stock (or common stock equivalents) offered in the registered direct offering (but not the warrants issued in the concurrent private placement or the shares of common stock underlying the warrants) are being offered and sold by Bio-Path pursuant to a "shelf" registration statement on Form S-3 (Registration No. 333-265282), including a base prospectus, previously filed with and declared effective by the Securities and Exchange Commission (SEC) on June 14, 2022. The offering of the shares of common stock (or common stock equivalents) will be made only by means of a prospectus supplement that forms a part of the registration statement. A final prospectus supplement and an accompanying base prospectus relating to the registered direct offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the prospectus supplement and accompanying base prospectus may also be obtained from Roth Capital Partners, LLC at [email protected].

Neither the warrants issued in the concurrent private placement nor the underlying shares of common stock issuable upon exercise of the warrants will be registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state securities laws. The warrants and the underlying shares of common stock issuable upon exercise of the warrants will be issued in reliance on the exemptions from registration provided by Section 4(a)(2) under the Securities Act and Regulation D promulgated thereunder. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

On November 7, 2022 Bicara Therapeutics, a clinical-stage biotechnology company developing dual-action biologics designed to modulate the tumor microenvironment to elicit a potent and durable anti-tumor response, reported preclinical data for BCA356, a bispecific designed to deliver safe and efficacious concentrations of an attenuated version of the pro-inflammatory cytokine IL-12 directly to the tumor microenvironment by targeting the tumor antigen carbonic anhydrase IX (CAIX) (Press release, Bicara Therapeutics, NOV 7, 2022, View Source;utm_medium=rss&utm_campaign=bicara-therapeutics-presents-preclinical-data-for-precision-immunocytokine-bca356-at-society-for-immunotherapy-of-cancer-sitc-2022-annual-meeting [SID1234623224]). These data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 37th Annual Meeting, being held in Boston, Massachusetts from November 8-12, 2022.

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!

"These data demonstrate BCA356’s potential to engage more difficult to treat, less immunogenic solid tumors by leveraging our engineered IL-12’s ability to locally activate the innate and adaptive immune system while avoiding the challenges seen with systemic IL-12 administration, such as cytokine release syndrome," said Claire Mazumdar, PhD MBA., Chief Executive Officer of Bicara Therapeutics. "These findings support our hypothesis that leveraging CAIX and attenuating IL-12 can offer a potentially safe and efficacious avenue for local IL-12 delivery because if its high expression in various tumor types and minimal expression in healthy tissues."

Bicara intends to continue advancing BCA356 through Investigational New Drug (IND)-enabling studies and expects to submit an IND application by the end of 2023.

BCA356 Data Highlights:

Immunohistochemistry studies confirm high CAIX expression across tumor types, notably in clear cell renal carcinoma.
BCA356 specifically targets CAIX-expressing tumor cells, and similar to wild type IL-12 cytokine, has the potential to reduce tumor proliferation with optimal activation of additional pro-inflammatory cytokines.
BCA356 attenuated IFNγ release by stimulated peripheral blood mononuclear cells (PBMCs), activated NK cell and pSTAT4 expression in CD8 T cells as compared to IL-12 wild type.
In co-culture assays, BCA356 demonstrated comparable cytotoxicity to wild type IL-12 without significant cytokine release.
Efficacy studies in humanized and transgenic mice models confirmed that BCA356 is efficacious and safe in CAIX-overexpressing tumor bearing mice.

On November 7, 2022 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported financial results for the third quarter, ended September 30, 2022 (Press release, Beam Therapeutics, NOV 7, 2022, View Source [SID1234623223]).

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!

"As pioneers in base editing, Beam has been at the forefront of advancing a broad pipeline across a range of therapeutic areas and delivery strategies, and today we report significant progress and updates in each of these areas," said John Evans, chief executive officer of Beam. "Our top priority is executing the BEACON trial for BEAM-101. Bringing a novel transplant-based medicine into clinical development in the U.S. has been a tremendous effort, and we are laser-focused on screening and site activation efforts to enroll our first sickle cell patient by year-end. We are also accelerating our overall BEAM-101 development program, where we see an opportunity to potentially seek regulatory approval on data generated from the BEACON trial. Given those priorities, we have elected not to file an IND in 2022 for BEAM-102. Instead, we will take the opportunity to streamline the BEACON trial while focusing the next phase of our investment in sickle cell disease on our Wave 2 programs for non-genotoxic conditioning, as well as our Wave 3 strategy for in vivo lipid nanoparticle delivery of base editors, continuing to leverage both HbF and Makassar editing strategies."

Evans added, "Beyond hematology, the Beam team has also executed on the rest of our ambitious goals for advancing and expanding our pipeline. In immune cell therapies, we have submitted our response to the FDA clinical hold for BEAM-201, and we continue our research toward a potential best-in-class platform for allogeneic cell therapies leveraging the strength of multiplex base editing, which may be the key to delivering deeper and more durable responses. In the liver portfolio, we have initiated IND-enabling studies for BEAM-301, to our knowledge the first gene editing program to target direct in vivo correction of a genetic mutation. Finally, we are very pleased to announce the selection of our second in vivo development candidate, BEAM-302, for alpha-1 antitrypsin deficiency (AATD). BEAM-302 is a first-in-kind program targeting direct in vivo DNA correction of the disease-causing E342K mutation in patients with severe AATD, which could address both the lung and liver manifestations of the disease with a potentially one-time treatment. I am so proud of the entire Beam team for advancing the science and medicine of base editing across such a diverse portfolio, and we are excited about the near-term opportunity to bring each of these potential medicines to patients."

Portfolio Updates & Anticipated Milestones
Ex Vivo Hematopoietic Stem Cell (HSC) Pipeline

Prioritization of BEAM-101 Clinical Execution: Beam continues to focus on development of BEAM-101, which upregulates the expression of fetal hemoglobin (HbF), as the lead program in its Wave 1 sickle cell disease (SCD) strategy to bring this medicine to patients as quickly as possible. Beam has activated multiple U.S. clinical trial sites, which are now recruiting patients for its BEACON trial, an open-label, single-arm, multicenter, Phase 1/2 clinical trial evaluating the safety and efficacy of BEAM-101 in adult patients with severe SCD. Per the BEACON trial protocol, once the first patient is enrolled, they will undergo a transfusion and mobilization process for HSC retrieval. The cells are then edited, creating an autologous BEAM-101 drug product. Following the drug product manufacturing, the patient will receive pre-treatment conditioning using a standard-of-care chemotherapy regimen, after which the edited cells are transplanted back into the patient. Following successful engraftment, treatment of a second patient can proceed. Beam continues to expect enrollment of the first patient in the BEACON trial by the end of 2022.

To accelerate development of BEAM-101, Beam is currently working to amend the BEACON trial protocol to enable clinical trial modifications designed to streamline and expedite patient enrollment and trial conduct based on the recent regulatory landscape in SCD trials. The company also plans to make investments required to finalize its commercial manufacturing process for BEAM-101.
Decision to Forgo BEAM-102 IND in 2022 and Optimize Program for Future SCD Waves: Beam has continued efforts in its Wave 2 strategy, which is designed to enable an improved, reduced-toxicity conditioning regimen for patients undergoing HSC transplantation, as well as its Wave 3 strategy, which is focused on in vivo delivery of base editors directly to HSCs. In connection with these efforts, Beam will not submit an investigational new drug (IND) application for BEAM-102, its base editing program designed to treat SCD by directly editing the causative HbS point mutation to create the naturally occurring normal human hemoglobin variant, HbG-Makassar, in 2022. Instead, the company plans to optimize its Makassar approach, alongside its HbF upregulation approach, as part of its future ex vivo and in vivo HSC candidates in Wave 2 and Wave 3 development, respectively.

Progress with Wave 2 Non-genotoxic Conditioning to be Reported at ASH (Free ASH Whitepaper): Beam plans to present new data on its improved conditioning technologies at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December. Beam has leveraged its base editing capabilities to develop a potentially non-genotoxic approach to SCD treatment that combines antibody-based conditioning with multiplex gene-edited HSCs called ESCAPE (Engineered Stem Cell Antibody Paired Evasion). ESCAPE-1 features the upregulation of fetal hemoglobin, the mechanism for BEAM-101, and ESCAPE-2 features HbG Makassar editing, the mechanism for BEAM-102.
Ex Vivo T Cell Pipeline

BEAM-201 IND Response Submitted to FDA: BEAM-201 is a first-in-kind, potent and specific anti-CD7, multiplex-edited, allogeneic chimeric antigen receptor T cell (CAR-T) development candidate. Beam submitted an IND for BEAM-201 to the FDA in June 2022, and in July 2022, was notified that the IND was placed on clinical hold. Beam has submitted its response to the FDA and will provide an update on next steps, as available.
In Vivo LNP Liver-targeting Pipeline

IND-enabling Studies Initiated for BEAM-301: BEAM-301 is designed to treat glycogen storage disease 1a (GSDIa), an autosomal recessive disorder caused by mutations in the G6PC gene that disrupt a key enzyme, glucose-6-phosphatase (G6Pase), critical for maintaining glucose homeostasis. Inhibition of G6Pase activity results in low fasting blood glucose levels that can result in seizures and be fatal. BEAM-301 is a liver-targeting lipid nanoparticle (LNP) formulation of base editing reagents designed to correct the R83C mutation, the most common disease-causing mutation of GSDIa.

BEAM-302 Named Development Candidate for Alpha-1 Antitrypsin Deficiency (AATD): Beam has nominated its second in vivo development candidate, BEAM-302, which it plans to develop as a potential one-time treatment to genetically correct the E342K point mutation (PiZZ genotype), which is most commonly responsible for severe AATD. AATD is a rare, inherited genetic disorder that can cause early onset emphysema and liver disease.

Patients with severe AATD (PiZZ) have accumulation of a non-functional protein in the liver (toxic gain of function) that causes liver damage and a decrease in circulating alpha-1 antitrypsin (AAT) (toxic loss of function) that results in lung damage due to insufficient inhibition of neutrophil elastase. Augmentation therapy with plasma-purified AAT is currently utilized in patients with lung disease and may slow lung function decline, but definitive data on long-term clinical outcomes, such as quality of life, frequency of exacerbations or survival, are limited. There are no FDA-approved therapies that can simultaneously treat AATD-related lung and liver disease.
In mouse models of AATD, LNP delivery of BEAM-302 was capable of efficiently correcting the PiZ mutation at clinically relevant doses of <1 mg/kg. Optimization of both the guide and editor for BEAM-302 has resulted in a greater than two-fold improvement in editing efficiency compared with previously published precursor reagents.
The increased level of mutation correction achieved with BEAM-302 increased secretion of functional AAT protein to levels that could be therapeutically relevant for protection of lung function in patients with AATD.
Prior precursor editors and guides have also demonstrated a corresponding reduction of toxic liver aggregates, suggesting the first-in-class potential of BEAM-302 to treat both lung and liver manifestations of the disease.
Beam has initiated preparations for preclinical manufacturing and preclinical development of BEAM-302.
First In Vivo Data for Multiplex Base Editing Approach to Treat Chronic HBV Infection: In September, Beam presented new preclinical data demonstrating the potential of the company’s multiplex base editing approach to both reduce viral markers – including hepatitis B surface antigen (HBsAg) expression – and prevent viral rebound of hepatitis B virus (HBV) in in vivo models.
Third Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1.1 billion as of September 30, 2022, as compared to $965.6 million as of December 31, 2021.
Research & Development (R&D) Expenses: R&D expenses were $85.3 million for the third quarter of 2022, compared to $54.6 million for the third quarter of 2021.
General & Administrative (G&A) Expenses: G&A expenses were $21.8 million for the third quarter of 2022, compared to $15.8 million for the third quarter of 2021.
Net Loss: Net loss was $109.6 million for the third quarter of 2022, or $1.56 per share, compared to $28.1 million for the third quarter of 2021, or $0.42 per share.