On August 8, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported financial results for the second quarter of 2023 and reviewed recent business updates (Press release, Caribou Biosciences, AUG 8, 2023, View Source [SID1234633959]).

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"In 2023, we have advanced our programs to build value across the pipeline and position Caribou for continued momentum ahead," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "For our lead program, we are excited by the positive CB-010 dose escalation data demonstrating response rates that rival those from the approved autologous CAR-T cell therapies. As we develop CB-010 for the larger second-line LCBL patient population, we continue to enroll patients in dose expansion and anticipate reporting initial dose expansion data in the first half of 2024. We also look forward to meeting with the FDA later this year to discuss a potential pivotal clinical trial in second-line LBCL patients. Additionally, we continue to enroll patients in our CaMMouflage trial for CB-011 and plan for an IND submission for CB-012 in the second half of this year."

Accomplishments and highlights

Pipeline and technology
•CB-010: Caribou reported [View Source long-term follow-up data from all 16 patients treated in dose escalation of the ongoing ANTLER Phase 1 clinical trial of CB-010, an allogeneic anti-CD19 CAR-T cell therapy. In ANTLER dose escalation, three dose levels of CB-010 were evaluated (40×106, 80×106, and 120×106 CAR-T cells) in patients with multiple subtypes of aggressive relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). As of the June 20, 2023 data cutoff date, results demonstrated:
◦CB-010 was generally well tolerated with adverse events consistent with autologous and allogeneic anti-CD19 CAR-T cell therapies.
◦94% overall response rate (ORR; 15 of 16 patients) was observed following a single dose of CB-010.
◦69% of patients (11 of 16) achieved a complete response (CR).

◦44% of patients (7 of 16) had a CR at ≥6 months; 24 months is the longest CR maintained to date.
◦For the subset of patients with large B cell lymphoma (LBCL) (N=10):
▪A 90% ORR (9 of 10) was observed.
▪70% (7 of 10) achieved a CR.
▪50% (5 of 10) had a CR at ≥6 months; 18 months is the longest CR maintained to date.
◦Based on these positive data, Caribou is enrolling second-line patients with LBCL in the ongoing dose expansion portion of the ANTLER clinical trial. In expansion, the mid dose and the high dose from escalation (80×106 and 120×106 CAR-T cells) are being evaluated in approximately 30 second-line patients (approximately 15 patients per dose level) to determine the recommended Phase 2 dose (RP2D). Once the RP2D is determined, Caribou may enroll additional patients in ANTLER.
•CB-011: Caribou is enrolling patients at dose level 1 (50×106 CAR-T cells) in the dose escalation portion of the ongoing CaMMouflage Phase 1 trial of CB-011, an allogeneic anti-BCMA CAR-T cell therapy, for relapsed or refractory multiple myeloma (r/r MM).
•CB-012: Caribou is advancing IND-enabling activities for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, for relapsed or refractory acute myeloid leukemia (r/r AML).

Anticipated milestones
•CB-010: Caribou plans to meet with the FDA to discuss a potential pivotal clinical trial in second-line LBCL patients and plans to share FDA feedback by YE 2023. The Company also plans to report initial dose expansion data in second-line LBCL patients from the ongoing ANTLER trial in H1 2024.
•CB-011: Caribou plans to provide updates on dose escalation as the CaMMouflage Phase 1 clinical trial in r/r MM advances.
•CB-012: Caribou plans to submit an IND application for r/r AML in H2 2023.

Corporate updates
•$25.0 million Pfizer investment: On June 30, 2023, Pfizer invested [View Source $25.0 million in Caribou common shares. In conjunction with the investment, Sriram Krishnaswami, PhD, joined Caribou’s scientific advisory board [View Source Caribou will use the proceeds from this investment to advance CB-011. Caribou maintains full ownership and control of CB-011 and its other allogeneic CAR-T and CAR-NK cell therapies.
•Completed successful $134.6 million follow-on financing: In the third quarter of 2023, Caribou completed an underwritten public offering of 22,115,384 shares of its common stock, which included the full exercise of the underwriters’ option to purchase additional shares. The approximate net proceeds to Caribou were $134.6 million.

Second quarter 2023 financial results

Cash, cash equivalents, and marketable securities: Caribou had $292.5 million in cash, cash equivalents, and marketable securities as of June 30, 2023, which included the $25.0 million proceeds from the Pfizer investment, compared to $317.0 million as of December 31, 2022. This amount does not include the approximately $134.6 million in net proceeds from the Company’s underwritten public offering completed in the third quarter of 2023. Caribou expects its cash, cash equivalents, marketable securities, and net proceeds from the recent public offering will be sufficient to fund its current operating plan into Q4 2025.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $3.8 million for the three months ended June 30, 2023, compared to $4.2 million for the same period 2022. The decrease was primarily due to a reduction in revenue recognized under the AbbVie Collaboration and License Agreement, partially offset by a revenue increase related to a veterinary therapeutics licensing agreement.
R&D expenses: Research and development expenses were $26.5 million for the three months ended June 30, 2023, compared to $22.6 million for the same period in 2022. The increase was primarily due to personnel-related expenses, including stock-based compensation; costs to advance pipeline programs, including the ANTLER and CaMMouflage Phase 1 trials; and facilities and other allocated expenses.

G&A expenses: General and administrative expenses were $10.1 million for the three months ended June 30, 2023, compared to $10.0 million for the same period in 2022. The increase was primarily due to facilities and other allocated expenses; patent prosecution and maintenance costs; and personnel-related expenses, including stock-based compensation, due to headcount increases. The increase was partially offset by lower insurance and legal expenses.
Net loss: Caribou reported a net loss of $29.5 million for the three months ended June 30, 2023, compared to $26.7 million for the same period in 2022.

About CB-010
CB-010 is the lead product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). In the ongoing ANTLER Phase 1 trial, Caribou is enrolling second-line patients with large B cell lymphoma (LBCL) comprising four different subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, and tFL). CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology. To Caribou’s knowledge, CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion. To Caribou’s knowledge, CB-010 is also the first anti-CD19 allogeneic CAR-T cell therapy to be evaluated in the second-line LBCL setting and it has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations by the FDA. Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov.

About CB-011
CB-011 is the second product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the CaMMouflage Phase 1 trial. CB-011 is an allogeneic anti-BCMA CAR-T cell therapy engineered using Cas12a chRDNA technology. To Caribou’s knowledge, CB-011 is the first allogeneic CAR-T cell therapy in the clinic that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M knockout and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection. CB-011 has been granted Fast Track designation by the FDA. Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

About CB-012
CB-012 is the third product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in investigational new drug (IND)-enabling studies. To Caribou’s knowledge, CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. CB-012 is engineered with five genome edits, enabled by Caribou’s patented next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits.

On August 8, 2023 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported financial results for the second quarter ended June 30, 2023, as well as recent business highlights (Press release, C4 Therapeutics, AUG 8, 2023, View Source [SID1234633958]).

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"In the first half of 2023, we achieved important objectives to support the continued advancement of our degrader medicine portfolio. We completed an exclusive licensing agreement with Betta Pharmaceuticals to develop CFT8919, our EGFR-L858R degrader, in Greater China, strengthened our leadership team, and progressed three clinical studies across multiple cancer indications," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "In the second half of the year, we expect to share clinical updates from the dose escalation portion of the ongoing Phase 1/2 trials for our two lead programs, CFT7455 in multiple myeloma and CFT8634 in synovial sarcoma and SMARCB1-null cancers."

SECOND QUARTER 2023 AND RECENT ACHIEVEMENTS

CFT7455: CFT7455 is an oral degrader of IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL).

Progressed the Phase 1/2 Clinical Trial: The dose escalation portion of the CFT7455 Phase 1/2 clinical trial continues in MM and NHL. The three arms of the trial are evaluating CFT7455 as a monotherapy for MM, in combination with dexamethasone for MM and as a monotherapy for NHL.
Presented New Preclinical Data at the International Conference on Malignant Lymphoma (ICML): In June 2023, C4T presented preclinical CFT7455 data in NHL demonstrating potent anti-tumor activity in peripheral and CNS models of NHL as a single agent or in combination with clinically approved agents.
CFT8634: CFT8634 is an oral degrader of BRD9 for the treatment of synovial sarcoma and SMARCB1-null solid tumors.

Progressed the Phase 1/2 Clinical Trial: The dose escalation portion of the CFT8634 Phase 1/2 clinical trial continues in synovial sarcoma and SMARCB1-null solid tumors.
Initiated the first enrichment cohort: In August, C4T initiated the first enrichment cohort to further assess pharmacodynamic and safety data. This planned additional cohort further helps support enrollment demand for the ongoing dose escalation portion of the CFT8634 Phase 1/2 clinical trial.
CFT1946: CFT1946 is an oral degrader targeting BRAF V600 mutations for the treatment of solid tumors including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and melanoma.

Progressed the Phase 1/2 Clinical Trial: The dose escalation portion of the CFT1946 Phase 1/2 clinical trial continues in V600 solid tumors, including NSCLC, CRC and melanoma. Trial sites are now open and enrolling patients in the U.S. and Europe.
Presented Trial in Progress Poster at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting: In June 2023, C4T presented a trial in progress poster titled "A Phase 1/2 Study of CFT1946, A Novel Bifunctional Degradation Activating Compound, or BiDAC Degrader, of Mutant BRAF V600 as Monotherapy and in Combination with Trametinib, in Mutant BRAF V600 Solid Tumors."
CFT8919: CFT8919 is an oral degrader designed to be potent and selective against EGFR L858R for non-small cell lung cancer (NSCLC).

Exclusive Licensing Agreement with Betta Pharmaceuticals in Greater China: In May 2023, C4T entered into an exclusive license and collaboration agreement for the development and commercialization of CFT8919 in Greater China, including Hong Kong SAR, Macau SAR and Taiwan. C4T expects to receive a total of $35.0 million, which includes $10.0 million in upfront cash paid in June 2023 under the collaboration agreement and a $25.0 million one-time equity investment under the stock purchase agreement. Additionally, C4T is eligible for up to $357.0 million in potential milestones and low to mid-double-digit percent royalties on net sales in the licensed territories.
Investigational New Drug (IND) Application Clearance Achieved: In June 2023, the U.S. Food and Drug Administration (FDA) cleared C4T’s IND application for CFT8919. C4T expects to initiate clinical trial activities outside Greater China following the completion of Betta Pharmaceuticals’ Phase 1 dose escalation study in Greater China.
CORPORATE UPDATES

In July 2023, C4T appointed two new senior leaders. Leonard (Len) Reyno, M.D., joined C4T as chief medical officer with nearly 30 years of clinical development experience, spanning first-in-human studies to Phase IV clinical trials. Mary Christian, Pharm.D. joined C4T as senior vice president, regulatory with more than two decades of experience in regulatory and drug development.
UPCOMING KEY MILESTONES

CFT7455: Present Phase 1 dose escalation data from the Phase 1/2 clinical trial of Arm B1, evaluating CFT7455 as a monotherapy in MM, in the second half of 2023.
CFT8634: Present Phase 1 dose escalation data from the Phase 1/2 clinical trial for synovial sarcoma and SMARCB1-null solid tumors in the second half of 2023.
SECOND QUARTER 2023 FINANCIAL RESULTS

Revenue: Total revenue for the second quarter of 2023 was $2.7 million, compared to $13.8 million for the second quarter of 2022. The decrease in revenue was due to a reduction of revenue recognized for research activities under the Biogen and Calico collaborations. Total revenue for the second quarter of 2023 reflects revenue recognized under collaboration agreements with Roche and Biogen, and total revenue recognized in the second quarter of 2022 reflects revenue recognized under collaborations agreements with Roche, Biogen, and Calico.

Research and Development (R&D) Expense: R&D expense for the second quarter of 2023 was $29.9 million, compared to $31.3 million for the second quarter of 2022. The reduction in R&D expense was primarily attributable to a decrease in IND-enabling activities as programs transition to the clinic.

General and Administrative (G&A) Expense: G&A expense for the second quarter of 2023 was $10.3 million, compared to $9.9 million for the second quarter of 2022. The higher G&A expense was attributable to a slight increase in professional fees.

Net Loss and Net Loss per Share: Net loss for the second quarter of 2023 was $35.9 million, compared to $27.4 million for the second quarter of 2022. Net loss per share for the second quarter of 2023 was $0.73 compared to $0.56 for the second quarter of 2022.

Cash Position and Financial Guidance: Cash, cash equivalents and marketable securities as of June 30, 2023, were $286.7 million, compared to $337.1 million as of December 31, 2022. The decrease in cash was primarily driven by expenditures to fund operations, partially offset by the $10.0 million upfront payment received from Betta Pharmaceuticals. C4T expects that its cash, cash equivalents and marketable securities as of June 30, 2023, along with the anticipated equity investment from an affiliate of Betta Pharmaceuticals, will be sufficient to fund planned operating expenses and capital expenditures into the second half of 2025.

On August 8, 2023 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird bio" or the "Company") reported financial results and business highlights for the second quarter ended June 30, 2023, including recent commercial and operational progress, and regulatory updates (Press release, bluebird bio, AUG 8, 2023, View Source [SID1234633956]).

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"As we approach the anniversaries of the FDA approvals of ZYNTEGLO and SKYSONA, we have continued to advance our commercial strategy and prove the model for the gene therapy field on our path to profitability," said Andrew Obenshain, chief executive officer, bluebird bio. "Additionally, with the ongoing FDA review of lovo-cel and potential approval by the end of this year, bluebird is preparing for our largest opportunity yet to impact the lives of patients and families – a gene therapy for individuals living with sickle cell disease in the US."

RECENT HIGHLIGHTS

ZYNTEGLO (betibeglogene autotemcel) Commercial Launch

bluebird continues to build on the launch of ZYNTEGLO for beta-thalassemia. To date, there have been 11 patient starts for ZYNTEGLO.
To date, the Company has received zero ultimate denials from commercial or government payers for ZYNTEGLO; prior authorization approvals for drug product remain consistent at approximately two weeks.
As previously communicated, patient starts remain the key commercial metric during the first year of the ZYNTEGLO launch.
SKYSONA (elivaldogene autotemcel) Commercial Launch

Cell collection has been completed for 5 patients for SKYSONA to date.
Since approval, bluebird has activated four QTCs to administer SKYSONA for patients with cerebral adrenoleukodystrophy (CALD).
lovo-cel BLA Acceptance and Priority Review

On June 21, 2023, bluebird bio announced that the FDA accepted for priority review its BLA for lovotibeglogene autotemcel (lovo-cel), the Company’s gene therapy for individuals living with sickle cell disease (SCD). bluebird is pursuing FDA approval for lovo-cel for patients ages 12 and older who have a history of vaso-occlusive events (VOEs). The agency has set a Prescription Drug User Fee Act (PDUFA) goal date of December 20, 2023.
lovo-cel ICER Review

In its ongoing review of the cost-effectiveness of gene therapies for sickle cell disease, the Institute for Clinical and Economic Review (ICER) determined that lovo-cel will be cost effective at a price up to $2.26 million when considering the societal perspective. bluebird anticipates setting a price for lovo-cel upon potential FDA approval.
UPCOMING ANTICIPATED MILESTONES

ZYNTEGLO

The Company is on track to scale to 40-50 QTCs by the end of 2023. bluebird’s QTC network is designed to maximize its commercial opportunity in beta-thalassemia and to prioritize proximity to individuals with living with SCD in anticipation of a 2024 commercial launch for lovo-cel, if approved by the FDA.
SKYSONA

The Company continues to anticipate 5-10 patient starts this year as previously guided.
LOVO-CEL

The FDA has set a PDUFA goal date for December 20, 2023, and if approved, the Company anticipates commercial launch in early 2024. bluebird estimates approximately 20,000 individuals living with SCD (or one-fifth of the U.S. SCD population) may be eligible for gene therapy.
SECOND QUARTER 2023 FINANCIAL RESULTS

Cash Position: The Company’s cash, cash equivalents, marketable securities and restricted cash balance was approximately $291 million, as of June 30, 2023. The Company anticipates full-year 2023 cash burn to be in the range of $270-$300 million, as previously guided. Based on current operating plans, bluebird expects its cash, cash equivalents, marketable securities and restricted cash, inclusive of revenue will be sufficient to meet bluebird’s planned operating expenses and capital expenditure requirements into the fourth quarter of 2024. Excluding $45 million of restricted cash, which is currently unavailable for use, bluebird estimates cash runway into the second quarter of 2024. Please see our Quarterly Report on Form 10-Q for the quarter ended June 30, 2023 for further information regarding our cash runway guidance and other financial results.
Revenue, net: Total revenue, net was $6.9 million for the three months ended June 30, 2023, compared to $1.5 million for the three months ended June 30, 2022. The increase of $5.4 million was primarily due to SKYSONA and ZYNTEGLO product revenue.
SG&A Expenses: Selling, general and administrative expenses were $40.3 million for the three months ended June 30, 2023, compared to $36.7 million for the three months ended June 30, 2022. SG&A includes lease expense related to 50 Binney Street; however, sublease income is presented in other income (expense), net. Excluding the lease expense for 50 Binney St., SG&A expenses were $30.7 million for the three months ended June 30, 2023, compared to $28.2 million for the three months ended June 30, 2022. This increase is mainly attributable to commercial costs driven by marketing activities for ZYNTEGLO and SKYSONA in the United States and the performance of commercial readiness activities in the United States for lovo-cel, in anticipation of potential approval, as well as costs related to employee compensation, benefits, and other head-count related expenses.
R&D Expenses: Research and development expenses were $42.3 million for the three months ended June 30, 2023, compared to $63.8 million for the three months ended June 30, 2022. The decrease of $21.5 million was primarily due to manufacturing costs related to SKYSONA and ZYNTEGLO now being included in inventory and cost of product revenue, as well as decreased employee compensation, benefit and other headcount-related expenses and a decrease in information technology and facility related costs in 2023.
Net income (loss): Net loss was $72.9 million for the three months ended June 30, 2023, compared to a net loss of $100.1 million for the three months ended June 30, 2022.
CONFERENCE CALL DETAILS

bluebird will hold a conference call to discuss second quarter financial results and commercial launch progress on Tuesday, August 8 at 8:00 am ET.

To access the call via telephone, please register at this link https://register.vevent.com/register/BI4fa1d86317c74333813f6827624e43ae to receive a dial in number and unique PIN to access the live conference call.

The live webcast of the call may be accessed by visiting the "Events & Presentations" page within the Investors & Media section of the bluebird website at View Source A replay of the webcast will be available on the bluebird website for 90 days following the event.

On August 8, 2023, bluebird bio, Inc. (the "Company") reported to have entered into an Open Market Sale AgreementSM (the "Sales Agreement") with Jefferies LLC ("Jefferies") to sell shares of the Company’s common stock, par value $0.01 per share (the "Common Stock"), with aggregate gross sales proceeds of up to $125.0 million , from time to time, through an "at the market" equity offering program under which Jefferies will act as sales agent (Filing, 8-K, bluebird bio, AUG 8, 2023, View Source [SID1234633955]).

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Under the Sales Agreement, the Company will set the parameters for the sale of shares, including any price, time or size limits or other customary parameters or conditions. Subject to the terms and conditions of the Sales Agreement, sales of Common Stock, if any, will be made by any method permitted that is deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended. The Company will pay Jefferies a commission equal to up to 3.0% of the gross proceeds of any Common Stock sold through Jefferies under the Sales Agreement, and also has provided Jefferies with customary representations, warranties, covenants and indemnification rights. The Sales Agreement may be terminated by the Company upon written notice to Jefferies or by Jefferies upon written notice to the Company, each upon ten trading days’ notice to the other party.

Any sales of shares under the Sales Agreement will be made pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-271772) filed with the Securities and Exchange Commission (the "Commission") on May 9, 2023, which was declared effective by the Commission on May 19, 2023. The Company filed a prospectus supplement with the Commission on August 8, 2023 in connection with the offer and sale of the shares pursuant to the Sales Agreement.

The foregoing is only a brief description of the material terms of the Sales Agreement and is qualified in its entirety by reference to the full agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference.

Latham & Watkins LLP, counsel to the Company, has issued an opinion to the Company, dated August 8, 2023, regarding the validity of the shares of Common Stock to be issued and sold pursuant to the Sales Agreement. A copy of the opinion is filed as Exhibit 5.1 to this Current Report on Form 8-K.

In addition, as previously disclosed, on June 22, 2022, the Company entered into an Equity Distribution Agreement (the "Equity Distribution Agreement") with Goldman Sachs & Co. LLC ("Goldman") to sell shares of Common Stock with aggregate gross sales proceeds of up to $75.0 million, from time to time, through an "at the market" equity offering program under which Goldman acted as sales agent.

On August 7, 2023, the Company delivered written notice to Goldman, effective as of such date, to terminate the Equity Distribution Agreement, pursuant to Section 8(a) thereof. The Company is not subject to any termination penalties related to the termination of the Equity Distribution Agreement. As of August 8, 2023, the Company has sold approximately 10.7 million shares of Common Stock under the Equity Distribution Agreement, resulting in gross proceeds to the Company of approximately $56.2 million.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of any offer to buy the securities discussed herein, nor shall there be any offer, solicitation or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On August 8, 2023 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported second quarter 2023 financial results and provided an update on its clinical and pipeline progress (Press release, Beam Therapeutics, AUG 8, 2023, View Source [SID1234633954]).

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"The first half of 2023 has been marked by focused execution across the business, with the singular goal of making an impact on the lives of people suffering from serious diseases," said John Evans, chief executive officer of Beam. "We are very pleased with the continued enrollment progress in the BEACON trial, having now consented enough patients projected to both fill the sentinel cohort and initiate the expansion cohort. In addition, the BEAM-201 trial is now open for enrollment at multiple clinical sites, with the first patient having been consented and dosing expected this quarter. We have also continued to accelerate development of BEAM-302, a potential best-in-class product candidate for patients with alpha-1 anti-trypsin deficiency, and are now prioritizing a BEAM-302 regulatory filing in the first quarter of 2024 as our first in vivo program, with a regulatory filing for BEAM-301 expected to follow shortly thereafter. Our critical manufacturing capability in North Carolina is anticipated to be cGMP ready for both cell manufacturing and LNP manufacturing this year. Finally, Beam is well capitalized to pursue the next wave of growth in its innovative research platform, from non-genotoxic conditioning with ESCAPE in hematology, to next-generation allogeneic cell therapies in cancer and immunology, to a growing number of wholly owned and partnered base editing programs targeting the liver. We believe we are well positioned to establish an industry-leading platform in precision genetic medicine."

Second Quarter 2023 Business Updates and Key 2023-2024 Anticipated Milestones

Hematology Portfolio

•
Beam continues to advance its BEACON Phase 1/2 clinical trial, an open-label, single-arm, multicenter study evaluating the safety and efficacy of BEAM-101 in adult patients with severe sickle cell disease (SCD).
o
Beam has continued to consent additional patients in the BEACON trial, all of whom are now moving in parallel through the screening, transfusion and mobilization activities required to enable treatment with BEAM-101.
o
Beam now anticipates that currently consented patients are sufficient to both fill the sentinel cohort (n=3) and to initiate the expansion cohort. Beam will continue adding additional patients to the BEACON trial through the end of year and beyond, with a total target of 45 treated patients.
o
Treatment with BEAM-101, in which the edited cell product is delivered in an autologous bone marrow transplant, will occur on a sequential basis for the first three patients treated in the trial, and then will be given in parallel for all subsequent patients.
o
The company continues to anticipate reporting initial data on multiple patients from the BEACON trial in 2024.
•
Beam continues to advance and invest in its Engineered Stem Cell Antibody Paired Evasion (ESCAPE) conditioning platform.

Immunology/Oncology Portfolio

•
Beam continues to advance BEAM-201, a multiplex-edited allogeneic CAR-T product candidate, for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL). Multiple sites for the Phase 1/2 clinical trial of BEAM-201 are now open for enrollment.
•
The first patient has consented and is expected to be dosed in the third quarter of 2023.
•
Beam also continues to invest in and advance its next-generation allogeneic strategies designed to improve cell persistence and expand the utility and accessibility of cell therapies in cancer and other diseases. The company plans to share updates on these efforts by year-end 2023.
Genetic Disease (in vivo) Portfolio

•
Beam continues to advance its two in vivo base editing product candidates, BEAM-301 for the treatment of glycogen storage disease 1a (GSD1a) and BEAM-302 for the treatment of alpha-1 antitrypsin deficiency (AATD), leveraging lipid nanoparticles (LNPs) for delivery to the liver.
•
To promote speed to the clinic of a top priority program, the company has leveraged the learnings and capability build from BEAM-301 to accelerate development of BEAM-302, which is now expected to be its first in vivo liver regulatory filing, followed by BEAM-301.
•
The company expects to:
o
Submit a regulatory application for authorization to initiate clinical trials for BEAM-302 in the first quarter of 2024; and
o
Submit a regulatory application for authorization to initiate clinical trials for BEAM-301 in the first half of 2024.
•
Beam continues to advance multiple additional in vivo editing programs targeting the liver, including both its wholly owned and collaboration programs, through lead optimization, and advance its LNP delivery technologies for delivery of base editing medicines to the liver and other tissues.
Manufacturing Updates

•
Beam continues to expect initiation of current good manufacturing practice compliant operations at its North Carolina manufacturing facility in late 2023.
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Beam is now planning to enable cGMP manufacturing of both autologous cell products in support of its sickle cell programs as well as LNP products in support of its liver programs BEAM-302 and BEAM-301 in its North Carolina facility.
Recent Nature Genetics Preclinical Publication Suggests Base Editing Enables More Uniform HbF Upregulation than Nuclease Editing

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In July, Beam co-founder David Liu, Ph.D., and St. Jude Children’s Research Hospital collaborators Jonathan Yen, Ph.D., and Mitchell Weiss, M.D., Ph.D., published preclinical research comparing five gene editing strategies in CD34+ hematopoietic stem and progenitor cells using either Cas9 nuclease or adenine base editors to induce fetal hemoglobin (HbF) red blood cells. Notably, the data suggest that base editing can provide a strategy for potent, uniform induction of HbF, yielding a consistent, predictable, and precise editing outcome. Conversely, nuclease editing of either the fetal hemoglobin gene or the BCL11A enhancer created a complex, uncontrolled distribution of alleles with a wide range of outcomes for induction of fetal hemoglobin, including numerous cells with minimal or no induction detected. These data illustrate the potential advantages of base editing’s mechanism of action, including the creation of predictable and consistent gene modifications with well-characterized, uniform biological effects across edited cells, as compared to the uncontrolled mixture of allele outcomes that result from nuclease-based knockout through double-stranded breaks.

Second Quarter 2023 Financial Results

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Cash Position: Cash, cash equivalents and marketable securities were $1.1 billion as of June 30, 2023, as compared to $1.1 billion as of December 31, 2022.
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Research & Development (R&D) Expenses: R&D expenses were $97.6 million for the second quarter of 2023, compared to $74.6 million for the second quarter of 2022.
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General & Administrative (G&A) Expenses: G&A expenses were $24.7 million for the second quarter of 2023, compared to $24.1 million for the second quarter of 2022.
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Net Loss: Net loss was $82.8 million for the second quarter of 2023, or $1.08 per share, compared to $72.0 million for the second quarter of 2022, or $1.02 per share.
Cash Runway

Beam expects that its cash, cash equivalents and marketable securities as of June 30, 2023, will enable the company to fund its anticipated operating expenses and capital expenditure requirements at least into 2025. This expectation includes funding directed toward reaching each of the key anticipated milestones for BEAM-101, BEAM-201, BEAM-301 and BEAM-302 described above, as well as continued investments in platform advancements and manufacturing capabilities.