APG-777

Apogee Therapeutics, an I&I biologics maker that quickly went public in 2023, said Monday it’s headed toward a Dupixent face-off next year as it looks to become the next “generational” biotech. The San Francisco company expects its lead drug APG777, an IL-13 targeting monoclonal antibody, can eventually generate more than $10 billion in sales, CEO Michael Henderson told Endpoints News in a preview of Apogee’s R&D day on Monday. The plan is to launch the medicine by the end of this decade, Henderson said. “Historically, people have thought about us as a YTE antibody, a longer-acting version of another antibody,” Henderson said, “and we’ve been making investments to become so much more than that, which is what we’re really excited to show at our R&D day.” Part of those grand ambitions are pinned on a combination future in inflammation and immunology. The I&I field has become one of the industry’s fastest-growing areas of R&D as drugmakers sling deals left and right for a market that Henderson said is only second in breadth to obesity. Apogee’s first big combination test will come next year as it pairs APG777 with its OX40L-targeting mAb called APG990. By way of a co-formulation, those experimental medicines will go up against Dupixent in 50 to 75 patients with moderate-to-severe atopic dermatitis in a Phase 1b, Apogee said. The readout is slated for the second half of 2026. “Everyone says, ‘Oh, we’re going to be better. It should be better,’” Henderson said. “No one ever actually runs that head-to-head study.” Dupixent has become a cornerstone of Sanofi and Regeneron’s I&I pipelines, with the medicine projected to break the $14 billion sales milestone this year. It also became the first biologic to get FDA approval for chronic obstructive pulmonary disease, or COPD, this fall. Apogee isn’t daunted. Its half-life technology, born out of its parent company Paragon Therapeutics, could allow for dosing every three or six months versus every two to four weeks for many other I&I therapies like Dupixent and Eli Lilly’s Ebglyss. Eventually, as part of lifecycle management, Henderson envisions a once-yearly dosing schedule. In 12-month Phase 1 data on Monday, Apogee said APG777 had a half-life of 77 days and “near complete” inhibition of pSTAT6 for up to 12 months with just one administration of the drug. “If we look at psoriasis, you have Skyrizi dosed every three months, and that started with an every two-week paradigm with Humira and then the IL-17s came out every four weeks,” Henderson said. “It’s too early to comment on price, of course, but in those cases, you see the price staying the same or even being higher with fewer injections because the better disease control and improved patient experience.” Enrollment is going so much faster than anticipated in Apogee’s Phase 2 trial of APG777 in atopic dermatitis that the company now plans to unveil 16-week Part A data from the study in mid-2025. That’s “months” earlier than the previously guided second half of next year, Henderson said. As a monotherapy, APG777 will also enter a Phase 1b in asthma by next summer, a Phase 2b in asthma in the second half of next year and a Phase 2 in eosinophilic esophagitis in 2026. The company’s combination plans also include pairing up APG777 with APG333, a mAb that goes after TSLP, which is targeted by Amgen’s Tezspire and candidates from a cohort of other biotechs . While Apogee plans to evaluate APG333 alone in a Phase 1b in asthma, its future relies on combinations with APG777 in asthma and COPD. “TSLP as a mono we are not excited about. People are doing that. It’s OK. But it’s crowded. It really is a combination that we get excited” about, Henderson said. Sanofi has an IL-13 and TSLP-targeting bispecific called lunsekimig, and Johnson & Johnson paid $850 million upfront for Proteologix and its bispecific in the arena. Apogee also said its Phase 1 healthy volunteer trial showed its drug APG808 had a half-life of about 55 days, which could translate to every two or three-month maintenance doses. The investigational IL-4Rα drug is also in a Phase 1b in asthma, with a readout planned for the first half of 2025. Apogee raised more than $400 million in a public offering in March on the back of interim Phase 1 healthy volunteer data. Will the company do it again after its R&D day? “We think that we’re incredibly undervalued right now, especially after the recent pullback in the market,” Henderson said. If the Phase 2 data are what Apogee is hoping for, then the company “should be able to access a much lower cost of capital than we’re at today,” he added. Apogee’s share price $APGE is down about 17% over the past month, but up 61% year-to-date. Henderson thinks the biotech is headed toward becoming a “generational” drugmaker like Vertex or Gilead. “They refuse to stop at good enough. They pursue combinations. They look to cannibalize their own markets,” Henderson said.

Continued execution across all programs, including positive results up to nine months from APG777 Phase 1 trial that continue to support potential best-in-class profile On track to report Phase 2 Part A data for APG777 in 2H 2025, interim Phase 1 data for APG808 in 4Q 2024 and interim Phase 1 data for APG990 in 1H 2025 APG333 development candidate selected and accelerating initiation of Phase 1 in late 2024 or early 2025; potential to offer best-in-class combination efficacy across multiple respiratory indications Plans advancing for combination studies, starting with the first clinical trial of the APG777 and APG990 combination for the treatment of AD in 2025 $754 million cash, cash equivalents and marketable securities with runway into 2028 Virtual R&D Day to be held December 2, 2024 at 10am ET SAN FRANCISCO and WALTHAM, Mass., Nov. 12, 2024 (GLOBE NEWSWIRE) -- Apogee Therapeutics, Inc., (Nasdaq: APGE), a clinical-stage biotechnology company advancing novel biologics with potential for differentiated efficacy and dosing in the largest inflammatory and immunology (I&I) markets, including for the treatment of atopic dermatitis (AD), asthma, chronic obstructive pulmonary disease (COPD) and other I&I indications, today reported pipeline highlights and third quarter financial results. “We continue to execute across our portfolio and advance potentially transformative therapies for patients living with I&I diseases by positioning our pipeline to achieve potential best-in-class efficacy and dosing,” said Michael Henderson, M.D., Chief Executive Officer of Apogee. “Over the past year, we demonstrated significant progress advancing three programs – soon to be four – into the clinic and our lead program, APG777, into Phase 2 trials. Importantly, we remain in a very strong cash position providing for runway into 2028 and look forward to sharing more details and progress on our pipeline and combination strategy during our R&D Day on December 2nd.” Pipeline Highlights and Upcoming Milestones Results up to 9 months from the APG777 Phase 1 trial reported at the American College of Allergy, Asthma and Immunology’s 2024 Annual Scientific Meeting (ACAAI) continue to support potential best-in-class profile, including a half-life of approximately 75 days: APG777 is a novel, subcutaneous (SQ) extended half-life monoclonal antibody (mAb) targeting IL-13 – a critical cytokine in inflammation and a primary driver of AD. At ACAAI, Apogee reported updated data from its Phase 1 trial in healthy volunteers, including findings from the 40 enrolled participants across three single-ascending dose cohorts, now with nine months of follow-up, and two multiple-ascending dose cohorts, now with six months of follow-up. Findings demonstrate that APG777, in single and multiple doses up to 1,200 mg, showed a consistent safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile following induction.PD profile showed near complete inhibition of pSTAT6 and sustained TARC inhibition up to 9 months.Updated data supports Apogee’s ongoing Phase 2 clinical trial of APG777 in AD demonstrating potential for improved clinical responses from greater exposures in induction and maintenance dosing of every 3- or 6-monthsThe company expects to report 16-week topline data from Part A of the APG777 Phase 2 trial in the second half of 2025. Phase 1 APG808 trial on track for 4Q 2024 interim data readout: APG808 is a novel SQ extended half-life mAb targeting IL-4Rα, a target with clinical validation across eight Type 2 allergic diseases. APG808 has similar binding affinity for IL-4Rα as a first generation mAb, DUPIXENT, and has demonstrated similar inhibition to DUPIXENT across three in vitro assays that measure downstream functional inhibition of the IL-13/IL-4 pathway. The company expects to report interim Phase 1 data for APG808 in the fourth quarter of 2024. First participants dosed in Phase 1 trial of APG990: APG990 is a novel, SQ half-life extended mAb targeting OX40L, initially being developed for AD. OX40L is located further upstream in the inflammatory pathway than IL-13 or IL-4Rα and targeting it could have broader impact on the inflammatory cascade by inhibiting Type 1, Type 2 and Type 3 pathways. In August 2024, Apogee initiated its Phase 1 APG990 trial, designed as a double-blind, placebo-controlled, first-in-human, single-ascending dose trial in healthy volunteers. The study will evaluate the safety, tolerability and PK of APG990 and is expected to enroll approximately 40 healthy adults across 5 cohorts.The company expects to report interim Phase 1 data for APG990 in the first half of 2025. Potential to expand patient reach with best-in-class efficacy and dosing with planned APG777 and APG990 combination approach, combining IL-13 and OX40L inhibition: Apogee plans to develop APG777 and APG990 together as a potential first-in-class coformulation combining deep and sustained inhibition of Type 2 inflammation via APG777's inhibition of IL-13 with broader inhibition of Types 1-3 inflammation through APG990's inhibition of OX40L. These combined mechanisms offer the potential for improved clinical responses over monotherapies across a variety of I&I diseases while the approach of co-formulating two extended half-life mAbs holds the potential for best-in-class dosing. The company plans to initiate the first clinical trial of the APG777 and APG990 combination in 2025. APG333 anti-TSLP antibody development candidate nominated: APG333 is a novel, SQ extended half-life mAb targeting thymic stromal lymphopoietin (TSLP). TSLP is an epithelial cell-derived cytokine that has emerged as an attractive validated target for the treatment of I&I indications. In addition, a TSLP-targeting mAb may be used in combination with other mAbs for potentially greater efficacy in broader populations. TSLP plays important roles in Type 2 and Type 3 inflammation, particularly in both eosinophilic and non-eosinophilic inflammation. TSLP inhibition has been clinically validated, with one approved product on the market for the treatment of severe asthma without biomarker or phenotype restrictions. Based on its mechanism, TSLP inhibition could offer treatment to the approximately 40% of severe asthma patients with low Type 2 inflammation. The company now plans to initiate a Phase 1 clinical trial in healthy volunteers of APG333 in late 2024 or early 2025.Pending Phase 1 data, the company has the opportunity to combine APG777 with APG333, combining IL-13 and TSLP inhibition, to drive potential best-in-class efficacy in asthma and other respiratory indications. Corporate Highlights Jeff S. Hartness appointed as Chief Commercial Officer. In September 2024, Apogee appointed Mr. Hartness as its Chief Commercial Officer. Mr. Hartness has an extensive track record in commercial and corporate leadership and more than 25 years of experience in the biotech industry focused on product launches, market access strategy, pricing and policy.Apogee Therapeutics 2024 Virtual R&D Day to be held on December 2, 2024 at 10am ET: The company plans to highlight its progress across its pipeline and showcase its path to reshaping the standard of care in I&I by bringing forward monotherapy and combination treatments that offer the potential for best-in-class efficacy and improved dosing. Third Quarter 2024 Financial Results Cash Position: As of September 30, 2024, Apogee had cash, cash equivalents and marketable securities of $753.8 million. Apogee expects that its existing cash will enable it to fund its current operating expenses into the first quarter of 2028.Research & Development (R&D) Expenses: R&D expenses for the third quarter of 2024 were $45.7 million, compared to $17.1 million for the third quarter of 2023. R&D expenses increased primarily due to further development of the company’s APG777, APG808, APG990 and APG333 programs and advancement of its pipeline into clinical trials, as well as increases in personnel costs, including equity-based compensation expense, associated with the growth of its R&D team.General and Administrative (G&A) Expenses: G&A expenses for the third quarter of 2024 were $13.0 million, compared to $7.2 million for the third quarter of 2023. G&A expenses increased primarily due to increases in personnel costs, including equity-based compensation, associated with the growth of the company’s G&A team, as well as increased costs related to being a public company, including for legal, IT and professional services, and to support the growth of the business.Net Loss: Net loss for the third quarter of 2024 was $49.0 million, compared to the net loss for the third quarter of 2023 which was $20.8 million. Net loss increased primarily as a result of higher R&D and G&A expenses as described above, partially offset by higher interest income. About ApogeeApogee Therapeutics is a clinical-stage biotechnology company advancing novel biologics with potential for differentiated efficacy and dosing in the largest inflammatory and immunology (I&I) markets, including for the treatment of atopic dermatitis (AD), asthma, chronic obstructive pulmonary disease (COPD) and other I&I indications. Apogee’s antibody programs are designed to overcome limitations of existing therapies by targeting well-established mechanisms of action and incorporating advanced antibody engineering to optimize half-life and other properties. APG777, the company’s most advanced program, is being initially developed for the treatment of AD, which is the largest and one of the least penetrated I&I markets. With four validated targets in its portfolio, Apogee is seeking to achieve best in class efficacy and dosing through monotherapies and combinations of its novel antibodies. Based on a broad pipeline and depth of expertise, the company believes it can deliver value and meaningful benefit to patients underserved by today’s standard of care. For more information, please visit https://apogeetherapeutics.com. Forward Looking StatementsCertain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, statements regarding: Apogee’s plans for its current and future product candidates and programs; the anticipated timing of the results from its clinical trials, including data from its Phase 2 trial of APG777, Phase 1 trial of APG808 and Phase 1 trial of APG990; the anticipated timing of initiation of its clinical trials, including its Phase 1 trial of APG333 and clinical trial of the APG777 and APG990 combination; its plans for current and future clinical trials; and the potential clinical benefit and half-life of APG777, Apogee’s other product candidates, and any other potential programs, including combination therapies; its expected timing for future pipeline updates and expectations regarding the time period over which Apogee’s capital resources will be sufficient to funds its anticipated operations. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While Apogee believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Apogee’s filings with the U.S. Securities and Exchange Commission (the SEC)), many of which are beyond the company’s control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of Apogee’s preclinical studies, clinical trials and research and development programs; expectations regarding the timing, completion and outcome of Apogee’s clinical trials; the unpredictable relationship between preclinical study results and clinical study results; the timing or likelihood of regulatory filings and approvals; liquidity and capital resources; and other risks and uncertainties identified in Apogee’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 5, 2024, Quarterly Report on 10-Q for the quarterly period ended June 30, 2024, filed with the SEC on August 12, 2024, and subsequent disclosure documents we may file with the SEC. Apogee claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Apogee expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. APOGEE THERAPEUTICS, INC.CONDENSED CONSOLIDATED BALANCE SHEETS(UNAUDITED)(In thousands, except unit/share data) SEPTEMBER 30,2024 DECEMBER 31,2023 Assets Current assets: Cash and cash equivalents $118,780 $118,316 Marketable securities 407,269 277,143 Prepaid expenses and other current assets 8,434 2,950 Total current assets 534,483 398,409 Long-term marketable securities 227,746 — Property and equipment, net 1,417 377 Right-of-use asset, net 12,126 2,217 Other non-current assets 514 401 Total assets $776,286 $401,404 Liabilities and stockholders' equity Current liabilities: Accounts payable $2,216 $2,143 Lease liability 2,867 1,101 Accrued expenses 27,528 17,314 Total current liabilities 32,611 20,558 Long-term liabilities: Lease liability, net of current 9,273 933 Total liabilities 41,884 21,491 Stockholders' equity: Common Stock; $0.00001 par value, 400,000,000 authorized, 58,509,583 issued and 56,899,295 outstanding as of September 30, 2024; 400,000,000 authorized, 50,655,671 issued and 48,338,769 outstanding as of December 31, 2023 1 — Additional paid-in capital 969,829 503,354 Accumulated other comprehensive income 3,270 329 Accumulated deficit (238,698) (123,770)Total stockholders’ equity 734,402 379,913 Total liabilities and stockholders’ equity $776,286 $401,404 APOGEE THERAPEUTICS, INC.CONDENSED CONSOLIDATED STATEMENT OF OPERATIONS(UNAUDITED)(In thousands) THREE MONTHS ENDED SEPTEMBER 30, NINE MONTHS ENDED SEPTEMBER 30, 2024 2023 2024 2023 Operating expenses: Research and development $45,714 $17,069 $107,636 $39,470 General and administrative 12,972 7,236 33,353 16,378 Total operating expenses 58,686 24,305 140,989 55,848 Loss from operations (58,686) (24,305) (140,989) (55,848)Other income, net: Interest income, net 9,668 3,465 26,061 3,598 Total other income, net 9,668 3,465 26,061 3,598 Net loss $(49,018) $(20,840) $(114,928) $(52,250) Investor Contact:Noel KurdiVP, Investor RelationsApogee Therapeutics, Inc.Noel.Kurdi@apogeetherapeutics.com Media Contact:Dan Budwick1AB Mediadan@1abmedia.com