On August 13, 2024 Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing a pipeline of novel therapies, reported its second quarter 2024 financial results and provided a corporate update (Press release, Instil Bio, AUG 13, 2024, View Source [SID1234645811]).

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"We have expanded our pipeline with a pair of clinical-stage, potentially best-in-class therapeutics by in-licensing SYN-2510 and SYN-27M," said Bronson Crouch, CEO of Instil. "By executing a 15-year lease of our Tarzana cell therapy manufacturing facility, we have strengthened our financial foundation to support Instil’s near-term clinical development of these assets."

Recent Highlights:

•In-licensed SYN-2510 and SYN-27M: In August 2024, SynBioTx, Inc., a wholly owned subsidiary of Instil, entered into a license and collaboration agreement with ImmuneOnco (HKEX:1541) for the exclusive global development and commercialization rights outside of Greater China of SYN-2510, a potentially best-in-class PD-L1xVEGF bispecific antibody, and SYN-27M, a next-generation ADCC-enhanced CTLA-4 antibody. SYN-2510 and SYN-27M have completed Phase 1a dose escalation studies in multiple solid tumor types in China, and ImmuneOnco is continuing patient enrollment in both programs to support dose optimization and dose expansion.

•Executed lease of our cell therapy manufacturing facility to AstraZeneca Pharmaceuticals LP: In July 2024, Instil reported the execution of a lease of its U.S. cell therapy manufacturing facility to AstraZeneca Pharmaceuticals LP. Under the terms of the agreement, initial base rent is greater than $7.5 million annually, and escalates at 3% per annum, with the tenant also required to pay certain operating expenses and tax expenses, subject to certain rent abatement in the first year of the 15-year lease term.

•Exploring further opportunities to in-license or acquire novel therapeutic candidates: Instil continues to explore further opportunities to in-license or otherwise acquire novel therapeutic candidates with first-in-class or best-in-class potential.
•Cash runway expected beyond 2026.

Second Quarter 2024 Financial and Operating Results:

As of June 30, 2024, Instil had cash, cash equivalents, marketable securities and long-term investments of $152.6 million, which consisted of $6.8 million in cash and cash equivalents, $141.8 million in marketable securities, and $4.0 million in long-term investments, compared to $175.0 million in cash, cash equivalents, marketable securities and long-term investments as of December 31, 2023, consisting of $9.2 million in cash and cash equivalents, $1.5 million in restricted cash, $141.2 million in marketable securities, and $23.2 million in long-term investments. Instil expects that its cash, cash equivalents, marketable securities and long-term investments as of June 30, 2024 will enable it to fund its operating plan beyond 2026.

Research and development expenses were $2.9 million and $10.2 million for the three and six months ended June 30, 2024, respectively, compared to $8.5 million and $29.1 million for the three and six months ended June 30, 2023, respectively.

General and administrative expenses were $10.7 million and $23.1 million for the three and six months ended June 30, 2024, respectively, compared to $11.5 million and $24.7 million for the three and six months ended June 30, 2023, respectively.

Restructuring and impairment charges were $0.5 million and $4.8 million for the three and six months ended June 30, 2024, respectively, compared to $1.0 million and $25.6 million for three and six months ended June 30, 2023, respectively.

Net loss per share, basic and diluted were $2.29 and $6.03 for the three and six months ended June 30, 2024, respectively, compared to $2.87 and $11.64 for the three and six months ended June 30, 2023, respectively. Non-GAAP net loss per share, basic and diluted, were $1.57 and $3.95 for the three and six months ended June 30, 2024, respectively, compared to $2.03 and $6.33 for the three and six months ended June 30, 2023, respectively.

On August 13, 2024 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported its financial results for the second quarter of 2024, its recent business highlights, and a preview of select anticipated milestones (Press release, Sutro Biopharma, AUG 13, 2024, View Source [SID1234645827]).

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"We continue to make meaningful progress with the development of luvelta across multiple indications, including enrollment of a patient expansion cohort in combination with bevacizumab, nearing initiation of our second registration-enabling trial, REFRaME-P1, for pediatric patients with a rare form of acute myeloid leukemia (AML) and approaching site activation of a Phase 2 trial in non-small cell lung cancer (NSCLC)," said Bill Newell, Sutro’s Chief Executive Officer. "We plan to share supplemental data from our Phase 1b trial of luvelta in combination with bevacizumab at the ESMO (Free ESMO Whitepaper) meeting in September."

Mr. Newell added, "We are off to strong start in our new partnership with Ipsen for STRO-003 and continue to advance our preclinical pipeline of next-generation ADCs, including our tissue-factor targeting exatecan ADC, STRO-004. In parallel, we are exploring new partnership opportunities to maximize the potential of our platform and pipeline, led by our new Chief Business Development Officer Barbara Leyman. Additionally, we are delighted to welcome Sukhi Jagpal to our Board, as he brings a wealth of invaluable financial and strategic expertise."

Recent Business Highlights and Select Anticipated Milestones

Luveltamab Tazevibulin (luvelta), FRα-Targeting ADC Franchise:

Sutro will present updated data from the Phase 1b study of luvelta in combination with bevacizumab for patients with ovarian cancer in a poster presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 to be held September 13-17 in Barcelona, Spain.
Title: Luveltamab tazevibulin, an antifolate receptor alpha (FRα) antibody-drug conjugate (ADC), in combination with bevacizumab (bev) in patients with recurrent high-grade epithelial ovarian cancer (EOC): STRO-002-GM2 phase 1 study
Date: Saturday, September 14, 2024
Part 2 (randomized portion) of the Phase 3 trial, REFRαME-O1, for treatment of platinum-resistant ovarian cancer (PROC), is underway.
REFRαME-P1, a registration-enabling trial for pediatric patients with CBFA2T3::GLIS2 (CBF/GLIS; RAM phenotype) AML, is expected to be initiated in the second half of 2024.
A Phase 2 expansion study in combination with bevacizumab is ongoing, with data expected in the first half of 2025.
A Phase 2 trial for the treatment of NSCLC is expected to initiate in the second half of 2024, with initial data expected in the first half of 2025.
Additional Pipeline Development and Collaboration Updates:

In April 2024, Sutro announced a global licensing agreement for STRO-003, a ROR1-targeting ADC, with Ipsen.
Sutro plans to submit an IND for STRO-004 in 2025.
Sutro continues to seek to maximize the value of its proprietary cell-free platform by working with partners on programs in multiple disease spaces and geographies and has generated from collaborators an aggregate of approximately $970 million in payments through June 30, 2024, including equity investments.
Corporate Updates:

In August, Sutro strengthened its Board of Directors with the appointment of Sukhi Jagpal, MBA, CPA, CBV. Mr. Jagpal brings 20 years of experience in the life sciences industry, with expertise in financial management, communication, and organizational effectiveness, including financial analysis, mergers and acquisitions, and cost optimization.
In July, Sutro appointed Barbara Leyman, Ph.D., as Chief Business Development Officer, with a focus on building value and executing the Company’s business development strategy, in addition to serving on Sutro’s senior management team.
Upcoming Events: Sutro will participate in two upcoming investor conferences. Webcasts of the presentations will be accessible through the News & Events page of the Investor Relations section of the Company’s website at www.sutrobio.com. Archived replays will be available for at least 30 days after the events.

Wedbush PacGrow Healthcare Conference in New York, August 13-14, 2024
Wells Fargo Healthcare Conference in Boston, September 4-6, 2024
Second Quarter 2024 Financial Highlights

Cash, Cash Equivalents and Marketable Securities and Vaxcyte Common Stock
As of June 30, 2024, Sutro had $426.0 million, composed of cash, cash equivalents and marketable securities of $375.6 million and approximately 0.7 million shares of Vaxcyte common stock with a fair value of $50.4 million.

Unrealized Gain from Increase in Value of Vaxcyte Common Stock
The non-operating, unrealized gain of $4.8 million for the quarter ended June 30, 2024 was due to the increase since March 31, 2024 in the estimated fair value of Sutro’s holdings of Vaxcyte common stock. Vaxcyte common stock held by Sutro will be remeasured at fair value based on the closing price of Vaxcyte’s common stock on the last trading day of each reporting period, with any non-operating, unrealized gains and losses recorded in Sutro’s statements of operations.

Revenue
Revenue was $25.7 million for the quarter ended June 30, 2024, as compared to $10.4 million for the same period in 2023, with the 2024 amount related principally to the Astellas collaboration and the Vaxcyte agreement. Future collaboration and license revenue under existing agreements, and from any additional collaboration and license partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones, and other agreement payments.

Operating Expenses
Total operating expenses for the quarter ended June 30, 2024 were $74.4 million, as compared to $56.6 million for the same period in 2023. The 2024 quarter includes non-cash expenses for stock-based compensation of $6.2 million and depreciation and amortization of $1.8 million, as compared to $6.7 million and $1.7 million, respectively, in the comparable 2023 period. Total operating expenses for the quarter ended June 30, 2024 were comprised of research and development expenses of $62.0 million and general and administrative expenses of $12.4 million.

On August 13, 2024 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company developing novel small molecule therapeutics to treat unmet needs in immune-mediated diseases and cancer, reported financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, Kezar Life Sciences, AUG 13, 2024, View Source [SID1234645812]).

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"We are thrilled to announce completion of enrollment to our PORTOLA trial and look forward to sharing topline results earlier than expected in the first half of 2025. This important milestone brings us one step closer to delivering zetomipzomib as a new treatment option for patients suffering from autoimmune hepatitis, a disease of significant unmet medical need," said Chris Kirk, PhD, Kezar’s Co-founder and Chief Executive Officer. "In addition, we are continuing to see strong enrollment activity in our global PALIZADE trial and look to continue this momentum by focusing our clinical resources on zetomipzomib development programs going forward. I want to thank our team for their hard work and commitment across all of our clinical trials and share our gratitude to the patients, their families and the study investigators, for their participation in these studies."

Zetomipzomib: Selective Immunoproteasome Inhibitor

PALIZADE – Phase 2b clinical trial of zetomipzomib in patients with active lupus nephritis (LN) (ClinicalTrials.gov: NCT05781750)

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PALIZADE is a global, placebo-controlled, randomized, double-blind Phase 2b clinical trial evaluating the efficacy and safety of two dose-levels of zetomipzomib in patients with active LN. Target enrollment will be 279 patients, randomly assigned (1:1:1) to receive 30 mg of zetomipzomib, 60 mg of zetomipzomib or placebo subcutaneously once weekly for 52 weeks, in addition to standard background therapy. Background therapy can, but will not be mandated to, include standard induction therapy. Over the initial 16 weeks, there will be a mandatory corticosteroid taper to 5 mg per day or less. End-of-treatment assessments will occur at Week 53. The primary efficacy endpoint is the proportion of patients who achieve a complete renal response (CRR) at Week 37, including a urine protein-to-creatine ratio (UPCR) of 0.5 or less without receiving rescue or prohibited medications.
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Our partner, Everest Medicines, announced that the first patient in China was dosed with zetomipzomib as part of our global PALIZADE trial. Kezar entered into a collaboration and license agreement with Everest Medicines in September 2023 to develop and commercialize zetomipzomib in Greater China, South Korea and Southeast Asia.

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Kezar expects to report topline data from PALIZADE in mid-2026.

PORTOLA – Phase 2a clinical trial of zetomipzomib in patients with autoimmune hepatitis (AIH) (ClinicalTrials.gov: NCT05569759)

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PORTOLA is a placebo-controlled, randomized, double-blind Phase 2a clinical trial evaluating the efficacy and safety of zetomipzomib in patients with AIH that are insufficiently responding to standard of care or have relapsed. The study has completed enrollment of 24 patients, randomized (2:1) to receive 60 mg of zetomipzomib or placebo in addition to background therapy for 24 weeks, with a protocol-suggested steroid taper. The primary efficacy endpoint will measure the proportion of patients who achieve a complete biochemical response by Week 24 measured as normalization of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and Immunoglobulin G (IgG) values (if elevated at baseline), with steroid dose levels not higher than baseline.
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Kezar expects to report topline data from PORTOLA in the first half of 2025.

KZR-261: Broad-Spectrum Sec61 Translocon Inhibitor

KZR-261-101– Phase 1 clinical trial of KZR-261 in patients with locally advanced or metastatic solid malignancies (ClinicalTrials.gov: NCT05047536)

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The Phase 1 clinical trial of KZR-261 is being conducted in two parts: dose escalation and dose expansion in tumor-specific solid tumors. The study is designed to evaluate safety and tolerability, pharmacokinetics and pharmacodynamics, identify a recommended Phase 2 dose and explore the preliminary anti-tumor activity of KZR-261 in patients with locally advanced or metastatic disease.
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Enrollment has been stopped in the KZR-261 Phase 1 study, and clinical resources are being reallocated toward development of zetomipzomib in AIH and LN. Patients already enrolled in the study will continue to have access to KZR-261.
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A total of 61 patients enrolled across the dose-escalation and dose expansion portions of the study, which included seven patients enrolled in the melanoma cohort of the dose-expansion portion at a dose level of 60 mg/m2.
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No objective responses have been observed to date in the study. Five patients (two with melanoma) within the dose escalation portion of the study experienced stable disease for four months or longer, of which two patients (melanoma; head and neck) experienced stable disease for twelve months or longer.
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KZR-261 has demonstrated consistent pharmacokinetics across all dose levels to date, and evidence of dose-dependent inhibition of Sec61 has been observed in patient blood samples.
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Kezar plans to report full data at a medical conference following completion of the study.

Financial Results

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Cash, cash equivalents and marketable securities totaled $164.2 million as of June 30, 2024, compared to $201.4 million as of December 31, 2023. The decrease was primarily attributable to cash used in operations to advance clinical-stage programs.

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Research and development (R&D) expenses for the second quarter of 2024 decreased by $4.7 million to $16.3 million, compared to $21.0 million in the second quarter of 2023. This decrease was primarily due to the Company’s strategic restructuring in October 2023 to prioritize its clinical-stage programs, reducing personnel-related costs and spending in its early-stage research activities. The decrease was partially offset by the increased clinical trial costs related to the PALIZADE and PORTOLA trials.
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General and administrative (G&A) expenses for the second quarter of 2024 decreased by $0.2 million to $5.6 million compared to $5.8 million in the second quarter of 2023. The decrease was primarily due to a decrease in legal and professional service expenses.
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Restructuring and impairment charges for the second quarter of 2024 were $1.5 million. The charges were primarily related to an impairment loss of the right-of-use asset related to vacated space in the company’s leased office facilities.
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Net loss for the second quarter of 2024 was $21.5 million, or $0.30 per basic and diluted common share, compared to a net loss of $24.3 million, or $0.34 per basic and diluted common share, for the second quarter of 2023.
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Total shares of common stock outstandingwere 72.9 million shares as of June 30, 2024. Additionally, there were options to purchase 15.3 million shares of common stock at a weighted-average exercise price of $2.18 per share and 0.2 million restricted stock units outstanding as of June 30, 2024.

On August 13, 2024 aTyr Pharma, Inc. (Nasdaq: ATYR) ("aTyr" or the "Company"), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, reported second quarter 2024 results and provided a corporate update (Press release, aTyr Pharma, AUG 13, 2024, View Source [SID1234645828]).

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"The second quarter of 2024 was a milestone quarter for aTyr, as we completed enrollment in our global pivotal Phase 3 EFZO-FIT study of efzofitimod in patients with pulmonary sarcoidosis, a major form of interstitial lung disease (ILD)," said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. "This landmark study is the largest interventional study ever to be conducted in sarcoidosis and presents an opportunity to deliver a potentially transformative therapy to sarcoidosis patients who have been waiting more than 60 years for a new drug to be approved for this disease. We look forward to releasing topline data from this study in the third quarter of 2025."

Second Quarter 2024 and Subsequent Period Highlights

Completed enrollment in the global pivotal Phase 3 EFZO-FIT study to evaluate the efficacy and safety of efzofitimod in patients with pulmonary sarcoidosis. This is a randomized, double-blind, placebo-controlled, 52-week study consisting of three parallel cohorts randomized equally to either 3.0 mg/kg or 5.0 mg/kg of efzofitimod or placebo dosed intravenously monthly for a total of 12 doses. The study enrolled 268 patients with pulmonary sarcoidosis at 85 centers in 9 countries, exceeding the targeted enrollment. Topline data from the study are expected in the third quarter of 2025. Patients who complete the study and wish to receive treatment with efzofitimod outside of the clinical trial are eligible to participate in an Individual Patient Expanded Access Program (EAP).
Continued enrollment in the Phase 2 EFZO-CONNECT study to evaluate the efficacy, safety and tolerability of efzofitimod in patients with systemic sclerosis (SSc, or scleroderma)-related ILD (SSc-ILD). This proof-of-concept study is a randomized, double-blind, placebo-controlled, 28-week study consisting of three parallel cohorts randomized 2:2:1 to either 270 mg or 450 mg of efzofitimod or placebo dosed intravenously monthly for a total of 6 doses. The study intends to enroll up to 25 patients with SSc-ILD and is open for enrollment at multiple centers in the U.S. Patients who complete the study and wish to receive ongoing treatment with efzofitimod are eligible to participate in a 24-week open-label extension (OLE), which was recently incorporated into the study protocol. Based on current enrollment projections, the Company expects to report interim data from the study in the second quarter of 2025.
Presented a poster describing efzofitimod’s mechanism of action at the American Thoracic Society (ATS) 2024 International Conference. The findings further demonstrated that neuropilin-2 (NRP2), efzofitimod’s binding partner, is an important new immune target in ILD and that efzofitimod modulates myeloid cells to confer its anti-inflammatory benefit.
Entered into a research agreement with Stanford Medicine to explore the role of the Company’s anti-NRP2 antibodies in glioblastoma multiforme (GBM). Michael Lim, M.D., Chair of the Department of Neurosurgery at Stanford Medicine, will serve as the principal investigator for the study, which aims to explore the role anti-NRP2 antibodies in combination with chemotherapy to evaluate their role in reversing immune evasion in GBM, the most common type of primary brain cancer.
Appointed Jayant Aphale, Ph.D., as Vice President, Technical Operations. Dr. Aphale has more than 30 years of experience working in technical operations and manufacturing for novel therapeutic and vaccine products at biotechnology and pharmaceutical companies. Dr. Aphale will serve as a member of the Company’s executive leadership team, overseeing manufacturing activities at contract development and manufacturing organizations and implementing strategies related to the continuous improvement of commercial manufacturing, supply chain management, process development of new products and product life cycle management.
Second Quarter 2024 Financial Highlights and Cash Position

Cash & Investment Position: Cash, cash equivalents, restricted cash and investments as of June 30, 2024, were $81.4 million.
R&D Expenses: Research and development expenses were $14.0 million for the second quarter 2024, which consisted primarily of clinical trial costs for the Phase 3 EFZO-FIT and Phase 2 EFZO-CONNECT studies, manufacturing costs for the efzofitimod program and research and development costs for the efzofitimod and discovery programs.
G&A Expenses: General and administrative expenses were $3.3 million for the second quarter 2024.
About Efzofitimod

Efzofitimod is a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease (ILD), a group of immune-mediated disorders that can cause inflammation and fibrosis, or scarring, of the lungs. Efzofitimod is a tRNA synthetase derived therapy that selectively modulates activated myeloid cells through neuropilin-2 to resolve inflammation without immune suppression and potentially prevent the progression of fibrosis. aTyr is currently investigating efzofitimod in the global Phase 3 EFZO-FIT study in patients with pulmonary sarcoidosis, a major form of ILD, and in the Phase 2 EFZO-CONNECT study in patients with systemic sclerosis (SSc, or scleroderma)-related ILD. These forms of ILD have limited therapeutic options and there is a need for safer and more effective, disease-modifying treatments that improve outcomes.

On August 13, 2024 Mereo BioPharma Group plc (NASDAQ: MREO) ("Mereo" or the "Company"), a clinical-stage biopharmaceutical company focused on rare diseases, reported its financial results for the second quarter ended June 30, 2024, and provided an update on recent corporate highlights (Press release, Mereo BioPharma, AUG 13, 2024, View Source [SID1234645813]). The Company reported cash and cash equivalents of $87.4 million as of June 30, 2024, which includes the net proceeds of the Company’s $50 million registered direct offering in June 2024. Mereo expects that this will provide cash runway into 2027, through multiple key inflection points.

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"We continued to make significant progress this quarter highlighted by additional positive data from the Phase 2 portion of the ongoing Phase 2/3 Orbit study in patients with OI," said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. "These data showed that the statistically significant annualized fracture rate reduction of 67% was maintained following treatment with setrusumab for at least 14 months of follow-up, further demonstrating the potential of setrusumab to generate long-term, clinically meaningful benefit for people living with OI. On alvelestat, we continue to work through the detailed regulatory submissions to ensure the AATD program is Phase 3-ready by the end of the year, in parallel with our ongoing discussions with multiple potential partners. With the proceeds from our June financing, we are well positioned through our key value inflection milestones and to support the ongoing pre-commercial activities essential for a successful launch of setrusumab in Europe following its potential approval."

Second Quarter 2024 Highlights, Recent Developments and Anticipated Milestones

Setrusumab (UX143)

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The Phase 3 Orbit and Cosmic studies of setrusumab in OI, conducted by our partner Ultragenyx, were fully enrolled as of April 30, 2024.

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On June 11, 2024, Mereo and Ultragenyx, announced positive 14-month results from the Phase 2 portion of the ongoing Phase 2/3 Orbit study (NCT05125809).

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The results from the Phase 2 portion of the Orbit study demonstrated that, as of the May 24, 2024 data cut-off date, treatment with setrusumab continued to significantly reduce incidence of fractures in patients with OI. Treatment with setrusumab also resulted in ongoing and meaningful improvements in lumbar spine bone mineral density (BMD) at month 12 without evidence of plateau.

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The median annualized rate of radiologically confirmed fractures across all 24 patients in the 2 years prior to treatment was 0.72. Following a mean treatment duration period of 16 months, the median annualized fracture rate was reduced by 67% to 0.00 (p=0.0014; n=24).

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The reduction in annualized fracture rates was associated with continued, clinically meaningful increases in BMD. At the 12-month time point, treatment with setrusumab resulted in a mean increase in lumbar spine BMD from baseline of 22% (p<0.0001, n=19) and an improvement of the lumbar spine BMD Z-score from a mean baseline of -1.73 to -0.49 at 12 months. The improvements in BMD and Z-scores were significant and consistent across all OI sub-types studied.

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As of the data cut-off date, there were no treatment-related serious adverse events observed in the study and no reported hypersensitivity reactions related to setrusumab.

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Research has been published from our osteogenesis imperfecta program: The 12-month results for the Phase 2b ASTEROID study in the Journal of Bone and Mineral Research and the first publication from SATURN (Systematic Accumulation of Treatment practices and Utilization, Real world evidence, and Natural history data for OI), which is expected to provide a coordinated data set across multiple treatment centers for OI across European countries, to support pricing and reimbursement decisions.

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More detailed data from the Phase 2 portion of the ongoing Phase 2/3 Orbit study will be presented at an upcoming scientific meeting

Alvelestat (MPH-966)

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The Company continues to engage with multiple potential partners for the development and commercialization for alvelestat in AATD

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At the end of Q2, Mereo submitted the initial validation work for SGRQ in AATD and the detailed Phase 3 package including the study protocol to the FDA in order to maintain the potential to start the Phase 3 study around the end of 2024.

Second Quarter 2024 Financial Results

Total research and development (R&D) expenses increased by $1.2 million, or 33%, from $3.7 million in the second quarter of 2023 to $4.9 million in the second quarter of 2024. The increase was primarily due to increases of $1.9 million and $0.9 million of R&D expenses for alvelestat and setrusumab, respectively, partially offset by a $1.5 million reduction in R&D expenses for etigilimab. The increase in the program expenses for alvelestat primarily relates to preparatory work for the Phase 3 study, including manufacturing and drug formulation activities, SGRQ validation activities and regulatory filings and interactions. The increase in program expenses for setrusumab is driven by additional activities in Europe and resources for the input into development, regulatory and manufacturing plans with our partner, Ultragenyx, as the global development program is funded by Ultragenyx pursuant to our license and collaboration agreement. The reduction in etigilimab expenses was primarily due to the winding down and completion during 2023 of the open label Phase 1b/2 basket study in combination with an anti-PD-1 in a range of tumor types.

General and administrative (G&A) expenses increased by $5.2 million from $2.7 million in the second quarter of 2023 to $7.9 million in the second quarter of 2024. The increase is primarily related to: (i) a $3.4 million reduction in expenses recognized in the second quarter of 2023 for amounts from our depository to reimburse certain expenses incurred by us in respect of our ADR program, whereas in 2024, $1.7 million was received from our depository in the first quarter of 2024; and (ii) pre-commercial activities to lay the foundation for the commercial launch of setrusumab in Europe, including those to support pricing and reimbursement by HTA authorities and payor decision-makers in Europe of $0.9 million.

Net loss for the second quarter of 2024 was $12.3 million, compared to $1.8 million during the second quarter of 2023, driven primarily by a one-time milestone payment of $9.0 million received in the second quarter of 2023, and increases in R&D expenses and G&A expenses in the second quarter of 2024.

As of June 30, 2024, the Company had cash and cash equivalents of $87.4 million, compared to $57.4 million as of December 31, 2023. This includes net proceeds of the $50 million underwritten registered direct offering priced at-the-market on June 14, 2024. The Company expects, based on current operational plans, that its existing cash and cash equivalents balance will enable it to fund its currently committed clinical trials, operating expenses including pre-commercial activities for setrusumab, and capital expenditure requirements into 2027. This guidance does not include any potential upfront payments associated with a partnership for alvelestat or business development activity around any of the Company’s non-core programs.

Total ordinary shares issued as of June 30, 2024, were 768,821,274. Total ADS equivalents as of June 30, 2024, were 153,764,254, with each ADS representing five ordinary shares of the Company.