8-K
Jade Biosciences, Inc. (JBIO)
8-K
2024-01-08
For: 2024-01-08
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April 10, 2026
UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 8, 2024
AEROVATE THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
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| Delaware | **** | 001-40544 | **** | 83-1377888 |
| (State or other jurisdiction | | (Commission | | (I.R.S. Employer |
| of incorporation) | | File Number) | | Identification No.) |
Aerovate Therapeutics, Inc.
930 Winter Street , Suite M-500 , Waltham , Massachusetts **** 02451
(Address of principal executive offices, including zip code)
( 617 ) 443-2400
(Registrant’s telephone number, including area code)
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
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| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
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| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
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☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
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| Title of each class | **** | Trade Symbol(s) | **** | Name of each exchange on which registered |
| Common Stock, $0.0001 par value per share | | AVTE | | The Nasdaq Global Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒
| Item 7.01 | Regulation FD Disclosure. |
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Aerovate Therapeutics, Inc. (the “Company”) is furnishing a corporate presentation, attached as Exhibit 99.1 to this Current Report on Form 8-K, which the Company intends to use from time to time in meetings with investors and others beginning on January 8, 2024. The corporate presentation will also be available in the “Events & Presentations” section of the Company’s website at https://ir.AerovateTx.com/events-presentations.
The information under this Item 7.01 of this Current Report on Form 8-K (including Exhibit 99.1) is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
| 99.1 | Corporate presentation of Aerovate Therapeutics, Inc., furnished herewith. | |
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| 104 | | Cover Page Interactive Data File |
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
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| | Aerovate Therapeutics, Inc. | |||
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| Date: January 8, 2024 | By: | /s/ Timothy P. Noyes | ||
| | | Timothy P Noyes | ||
| | | Chief Executive Officer |
Exhibit 99.1
| Meaningfully Improving the Lives of<br>Patients with Rare<br>Cardiopulmonary Disease<br>Targeting the Hyperproliferative Cause<br>of Pulmonary Arterial Hypertension<br>January 2024<br>Nasdaq: AVTE |
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| This presentation has been prepared by Aerovate Therapeutics, Inc. ("we," "us," "our," "Aerovate" or the “Company”) and is made for informational purposes only. The<br>information set forth herein does not purport to be complete or to contain all of the information you may desire. Statements contained herein are made as of the date of this<br>presentation unless stated otherwise, and this presentation shall not under any circumstances create an implication that the information contained herein is correct as of any<br>time after such date or that information will be updated or revised to reflect information that subsequently becomes available or changes occurring after the date hereof.<br>The following presentation contains forward-looking statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995.<br>Forward-looking statements can be identified by words such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “future,” “goal,” “intend,” “look forward to,” “may,”<br>“plan,” “potential,” “predict,” “project,” “seek,” “strategy,” “should,” “will,” “would” and similar expressions regarding future periods. These forward-looking statements<br>include, but are not limited to, statements regarding Aerovate’s business plans and objectives; future plans for AV-101, including expectations regarding timing and success of<br>the planned clinical trial, therapeutic potential, clinical benefits and safety thereof; growth as a company; the potential value and market for AV-101; and uses and need of<br>capital, expenses and other financial results currently or in the future. These forward-looking statements are not promises or guarantees and involve substantial risks and<br>uncertainties and are based on our current beliefs, expectations and assumptions regarding future conditions. Because forward-looking statements relate to the future, they<br>are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and<br>financial condition may differ materially from those indicated in the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements.<br>Among the factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this<br>presentation are those risks and uncertainties, without limitation, associated with the following: the impact of the COVID-19 pandemic on the company’s business, operations,<br>patient enrollment and retention, strategy, goals and anticipated milestones; the therapeutic potential of AV-101, and the timing associated with the initiation, continuation or<br>success of Aerovate’s ongoing or planned clinical trials of AV-101; Aerovate’s ability to execute on its strategy; positive results from a preclinical or clinical study may not<br>necessarily be predictive of the results of future or ongoing clinical studies; AV-101 may not be successfully developed and commercialized; regulatory developments in the<br>United States and foreign countries; Aerovate’s ability to protect and maintain its intellectual property position; as well as those risks and uncertainties set forth more fully<br>under the caption "Risk Factors" in our Quarterly Report on Form 10-Q, as well as other risks detailed in our subsequent filings with the United States Securities and Exchange<br>Commission (SEC). Any forward-looking statement made by us is based only on information currently available to us and speaks only as of the date on which it is made. We<br>undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new<br>information, future developments or otherwise.<br>Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company’s<br>own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this presentation, it has not independently verified,<br>and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, all of the market data<br>included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally,<br>while we believe our own internal research is reliable, such research has not been verified by any independent source.<br>2<br>Disclaimer; Forward-Looking Statements |
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| Experienced Management Team<br>3<br>Ben Dake, PhD<br>President & Founder<br>• Entrepreneur, Cancer Biologist<br>and Investor<br>• Conceptualized AV-101 and<br>secured up to $79M in financing<br>for Aerovate<br>Hunter Gillies, MB ChB<br>Chief Medical Officer<br>• Led AMBITION trial for Gilead<br>that established current first-line<br>PAH combination therapy<br>• Led successful Phase 2 and 3<br>trials for PAH product candidates<br>at Pfizer and Gilead<br>Ralph Niven, PhD<br>Chief Development Officer<br>• 25 years’ broad expertise in<br>translational medicine and<br>inhalation dosage forms<br>• Managed experimental and<br>clinical development at<br>public and private<br>companies, including Amgen,<br>AIR and Novartis<br>Timothy Noyes<br>Chief Executive Officer<br>• 30 years’ commercial<br>experience in pharma and<br>biotech, including Merck,<br>Genzyme, Proteon<br>• Extensive launch planning<br>and commercial launch<br>experience<br>George Eldridge<br>Chief Financial Officer<br>• 25 years’ experience in<br>biotech, with both public<br>and private companies,<br>including Curis, Targanta,<br>Proteon<br>• Extensive background<br>raising capital in private,<br>IPO and follow-on<br>settings, investment<br>banking and M&A<br>Timothy Pigot<br>Chief Commercial Officer<br>• 25 years’ experience in<br>biotech and pharma<br>working to launch and<br>commercialize a range of<br>products<br>• 10 years’ experience in<br>PAH overseeing the US<br>launches of Revatio and<br>Leairis while at Pfizer<br>and Gilead Sciences,<br>respectively<br>Susan Fischer<br>SVP, Clinical Ops.<br>• 20 years’ experience in<br>clinical operations in<br>both academic and the<br>pharmaceutical<br>industry.<br>• Previously built/led<br>clinical ops teams at<br>Syndax, EMD Serono,<br>Acetylon<br>Donna Dea<br>Head of Regulatory<br>• 35 years of pharmaceutical<br>experience at AstraZeneca<br>• 20 years of global regulatory<br>experience designing/<br>implementing strategies resulting<br>in approval of treatments for<br>asthma, COPD, rhinitis and others<br>Marco Verwijs<br>Chief Technical Officer<br>• 15 years’ experience<br>developing drugs from<br>clinical product<br>development thru<br>commercial launch<br>• Proven leader in drug<br>product scale-up and<br>validation. |
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| Significant Unmet<br>Need<br>Despite three drug<br>classes approved,<br>5-year survival for<br>newly diagnosed PAH<br>patients is 61%<br>Demonstrated<br>Clinical Benefit<br>The molecule in AV-101, imatinib, already<br>has shown clinical<br>benefit in a Phase 3<br>clinical trial<br>conducted by<br>Novartis of oral<br>imatinib mesylate in<br>PAH patients on top<br>of two or more<br>standard of care<br>therapies.<br>Unfortunately, AEs<br>with oral imatinib<br>were common and<br>development was<br>discontinued<br>Efficient Execution<br>FDA and EMA orphan<br>designation for AV-101<br>for the treatment of<br>PAH<br>Phase 1 SAD/MAD in<br>healthy volunteers<br>complete<br>Phase 2b dose-ranging<br>portion of a Phase<br>2b/3 trial in PAH<br>patients. Ph2b portion<br>fully enrolled with<br>Ph2b data expected in<br>June 2024<br>Established Market<br>$6B+ market, yet<br>outcomes are poor<br>Aerovate: An Inventive Way Forward in PAH<br>4<br>Inventive<br>Solution<br>Anti-proliferative<br>targeted inhaled dry<br>powder PAH product<br>candidate AV-101<br>designed to provide<br>robust clinical benefit<br>of imatinib without<br>systemic AEs<br>observed with oral<br>imatinib |
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| Comfortable at rest, but<br>ordinary physical activity<br>causes shortness of<br>breath, fatigue, chest pain,<br>fainting<br>Comfortable at rest, but<br>less than ordinary physical<br>activity causes shortness of<br>breath, fatigue, chest pain,<br>fainting<br>Symptoms at rest.<br>Overt heart failure<br>No<br>limitation<br>Relentless Disease Progression<br>Impairs Daily Life<br>5<br>Activity<br>limited<br>Marked<br>limitation<br>Severe<br>limitation<br>Despite standard of care (SOC) most patients progress to overt heart failure |
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| 6<br>~ 70,000<br>People with PAH<br>in the US/EU<br>~ 35,000<br>People with PAH<br>in the US<br>$6B+<br>Global annual drug<br>spending<br>65-80%<br>Female<br>61-65%<br>5-year survival<br>Newly diagnosed and<br>prevalent patients<br>53 years<br>Average age at<br>diagnosis<br>Pulmonary Arterial Hypertension |
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| Patient Outcomes Are Poor Despite $6B+<br>PAH Vasodilator Market<br>7<br>NO pathway<br>$0.7B<br>ERAs<br>$2.3B<br>Prostanoids<br>$3.0B<br>SOC<br>Vasodilators<br>5-year survival<br>61-65%<br>for newly diagnosed and<br>prevalent patients<br>~65% patients take<br>2-3 drugs<br>No approved PAH therapy primarily addresses<br>abnormal cellular proliferation |
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| Reinventing Imatinib From a Cancer<br>Drug to a Potential PAH Therapy<br>88 |
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| 9<br>Phase 3 IMPRES Trial: Oral Imatinib Demonstrated<br>Improvement on Top of Maximal Background<br>(Adapted from Circulation. 2013;127:1128-1138.)<br>Change in 6MWD from baseline (m)<br>Time (weeks)<br>0 4 8 12 16 20 24<br>32m<br>0<br>10<br>20<br>30<br>40<br>50<br>60<br>70<br>*<br>*<br>*<br>*<br>Imatinib<br>Placebo<br>*P<0.05<br>Novartis global Phase 3 trial<br>(n=202) of oral imatinib<br>Required to be on at least 2 SOC<br>PAH drugs<br>WHO functional class II- IV<br>Statistically significant and clinically<br>meaningful benefit on primary<br>endpoint 6MWD after 24 weeks<br>6MWD is an accepted endpoint for<br>approval in PAH |
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| Phase 3 IMPRES Trial: Benefit Consistent Across<br>Secondary Endpoints<br>Secondary Endpoints (24wk)<br>Demonstrated robust hemodynamic effect<br>(A) Decreased mean pulmonary artery pressure<br>(B) Increased cardiac output<br>(C) Pulmonary vascular resistance (PVR) dropped<br>32% (P < 0.001), a validated efficacy endpoint<br>typically used for dose-finding<br>(D) Right atrial pressure lowered<br>10<br>Aerovate’s Phase 2b trial will use PVR<br>as the primary endpoint<br>(Circulation. 2013;127:1128-1138.) |
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| Imatinib<br>n=103 (%)<br>Placebo<br>n=98 (%)<br>Adverse Event + 100 (97) 94 (96)<br>Nausea 57 (55) 23 (24)<br>Peripheral edema 45 (44) 20 (20)<br>Diarrhea 36 (35) 19 (19)<br>Vomiting 31 (30) 10 (10)<br>Periorbital edema 30 (29) 7 (7)<br>Headache 25 (24) 22 (22)<br>Dyspnea 19 (18) 13 (13)<br>Nasopharyngitis 18 (18) 19 (19)<br>Hypokalemia 16 (16) 3 (3)<br>Anemia 14 (14) 3 (3)<br>Cough 11 (11) 15 (15)<br>Fatigue 11 (11) 7 (7)<br>Face edema 10 (10) 1 (1)<br>Muscle spasms 10 (10) 2 (2)<br>Imatinib<br>n=103 (%)<br>Placebo<br>n=98 (%)<br>Serious Adverse Event + 45 (44) 29 (30)<br>Worsening of pulmonary hypertension 6 (6) 8 (8)<br>Anemia 7 (7) 1 (1)<br>Dyspnea 6 (6) 2 (2)<br>Peripheral edema 6 (6) 0<br>Presyncope 5 (5) 0<br>Diarrhea 3 (3) 2 (2)<br>Device-related infection 3 (3) 0<br>Syncope 1 (1) 5 (5)<br>Subdural hematoma * 2 (2) 0<br>Oral Imatinib Caused Systemic Adverse Events<br>11<br>(Circulation. 2013;127:1128-1138.)<br>* In long-term extension portion of the trial, 6 additional<br>patients experienced a subdural<br>hematoma.<br>+ Individual adverse events are shown if they occurred in >10% in the imatinib group. Individual serious adverse events are shown if<br>they occurred in ≥3 patients in either group. |
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| AV-101<br>Potential Targeted Treatment for PAH<br>1212 |
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| 13<br>AV-101<br>AV-101 is a combination product<br>comprised of a proprietary dry powder<br>imatinib formulation in a capsule<br>delivered by a dry powder inhaler<br>designed to:<br>• Deliver drug to the lungs<br>• Limit systemic exposure<br>• Be easily administered<br>Imatinib molecular structure unmodified |
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| PAH is a Disease of All Layers of the Pulmonary Arteries<br>14<br>1. Adapted from J Am Coll Cardiol. 2015 May 12;65(18):1976-97. 2. Eur Respir J. 2019 Jan 24;53(1):1801887. 3. J Appl Physiol (1985). 2011 Apr;110(4):1119-29.)<br>Latex cast of human airway<br>(white), arterial tree (red),<br>and venous tree (blue)3<br>1 |
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| 15<br>AV-101 Phase 1 Trial<br>A single and multiple ascending dose Phase 1 study (n=82) in healthy volunteers to determine<br>safety and tolerability<br>MAD<br>n=12 per cohort; 9 Active / 3 Placebo<br>Low dose 10 mg<br>Med dose 30 mg<br>High dose 90 mg<br>Seven days of BID dosing<br>SAD STUDY ASSESSMENTS<br>n=8 per cohort<br>Five AV-101 cohorts from<br>1 mg to 90 mg<br>400 mg imatinib tablet for systemic<br>exposure comparison<br>Vital Signs<br>Pulmonary Function Testing<br>(FEV1 and FVC)<br>Oxygen Saturations<br>QTc<br>Adverse Events<br>n=6 Active / 2 Placebo<br>n=8 |
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| 16<br>AV-101 Phase 1 Trial: Lower Systemic Exposures Observed<br>0<br>500<br>1000<br>1500<br>2000<br>2500<br>0 12 24<br>Imatinib plasma concentration (ng/ml)<br>Hours post-dose<br>Plasma levels of AV-101 at final dose (steady state)<br>400 mg oral simulated<br>steady state<br>90 mg AV-101 day 7<br>90 mg projected additional<br>dose to simulate BID<br>30 mg AV-101 day 7<br>10 mg AV-101 day 7<br>Systemic exposures for all doses of AV-101 observed to be lower than simulated steady-state<br>exposure of 400 mg of oral imatinib |
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| 17<br>AV-101 Phase 1 Tolerability Profile<br>AV-101 was generally well tolerated<br>• No serious adverse events were reported<br>• No change in pulmonary function, oxygen<br>saturation, and QTc interval<br>• Most AEs mild to moderate<br>• One discontinuation due to vomiting on Day 1 in<br>the MAD 90 mg Cohort<br>• Most common AE, cough, was at max dose and<br>limited to within 30 minutes of dosing<br>Adverse Event<br>n(%)<br>10 mg<br>(n=8)<br>30 mg<br>(n=9)<br>90 mg*<br>(n=9)<br>Cough 1 (13) 1 (11) 5 (56)<br>Persistent cough - - -<br>Headache - - 4 (44)<br>Nausea - - 2 (22)<br>Chest discomfort - - 2 (22)<br>Throat irritation - 1 (11) 1 (11)<br>Musculoskeletal pain - - 2 (22)<br>Single incidence AEs: Vomiting (discontinued), Dysgeusia, Musculoskeletal chest pain,<br>Nasal congestion, Oropharyngeal pain, Back pain, Abdominal pain, Covid-19, Presyncope,<br>Alanine aminotransferase increased<br>*90mg dose was administered as 9 x 10mg capsules |
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| Phase 2b Dose-Ranging Trial<br>• Placebo controlled dose-ranging study<br>– 10 mg, 35 mg and 70 mg AV-101 BID for 24 weeks<br>– Targeting 200 patients across 4 dose groups<br>• Multicenter international trial<br>• Two or more background PAH therapies<br>• Functional class II - IV<br>• Primary endpoint: change in pulmonary vascular resistance (PVR) at<br>24 weeks<br>– Statistically significant improvement on PVR already demonstrated<br>with oral imatinib in multiple third-party clinical trials<br>– Validated endpoint<br>– Powered to detect statistically significant change<br>• Key secondary endpoints: Change in 6MWD, NTproBNP, QoL<br>18 |
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| 19<br>Expected AV-101 Lung Exposures of Planned Phase 2b<br>Doses, Extrapolated based on Phase 1 Results<br>0<br>5000<br>10000<br>15000<br>20000<br>25000<br>0 12 24<br>Imatinib lungs concentration (ng/ml)<br>Hours post-dose<br>70 mg AV-101<br>35 mg AV-101<br>10 mg AV-101<br>400 mg oral<br>Predicted lung concentrations of planned Phase 2b doses of AV-101 overlap or surpass 400 mg oral imatinib<br>dose. Predicted lung concentrations extrapolated based on a PK model using published method for the<br>extrapolation of lung exposures, based on plasma levels observed in Phase 1 trial |
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| Phase 2b Phase 3<br>Phase 2b/3 Adaptive Continuous Trial of AV-101<br>20<br>• All patients are treated for 24 weeks<br>• 6MWD is primary endpoint in Phase 3<br>• Phase 3 enrollment begins immediately upon completion of Phase 2b enrollment<br>• Phase 3 dose selected based on Phase 2b data after 24 weeks of follow up<br>PART 1 PART 2 PART 3<br>10 mg (n=50)<br>35 mg (n=50)<br>70 mg (n=50)<br>placebo (n=50)<br>10 mg<br>35 mg<br>70 mg<br>Placebo<br>Continue Optimal Dose |
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| PAH Trials with Non-Vasodilatory MOAs:<br>21<br>Oral Imatinib Merck/Acceleron<br>Sotatercept (activin trap)<br>Gossamer<br>Seralutinib (TKI)<br>IMPRES (Ph3) PULSAR (Ph2) STELLAR (Ph3) TORREY (Ph2)<br>low high<br>PVR -31.8% -20.5% -33.9% -30.7% -14.3%<br>6MWD +32 m<br>p=0.002<br>+29 m<br>p=0.02<br>+21 m<br>p=0.08<br>+40.8 m<br>p=0.001<br>*median<br>+6.5m<br>p=0.597<br>PAH Clinical Pipeline For Novel Mechanisms is Limited<br>Other Potential Non-Vasodilator<br>PAH Therapies in Clinical<br>Development:<br>• Aerami/Philip Morris – AER-901<br>(nebulized imatinib)<br>Phase 1 complete<br>• Sumitomo (Enzyvant) –<br>Rodatristat (tryptophan<br>hydroxylase inhibitor) in<br>Phase 2 (Failed Trial)<br>The data in the chart above are based on a cross-trial comparison and not a head-to-head clinical trial. Such data may not be directly<br>comparable due to differences in trial design, study protocols, conditions and patient populations. |
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| AV-101: Potential to Be An Ideal Add-On Agent<br>• Al Launch, AV-101 potential to be an ideal add on agent*<br>– Compelling clinical profile in combination with current therapies<br>– Simplicity and ease-of-use<br>– Potential to be part of the future standard of care<br>• Potential positioning within target populations*<br>– In front of inhaled and oral prostacyclin therapy<br>– In front of sotatercept for patients sotatercept ineligible patients<br>and patients who prefer inhalation vs injection<br>– Patients who remain at moderate to high risk of poor outcomes<br>despite sotatercept and prostacyclin therapy<br>– Patients who do not tolerate sotatercept and prostacyclin<br>therapy<br>22<br>*Assumes data and FDA discussions support FDA approval with supportive labeling |
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| AVTE’s Perspective on Current And Future PAH Landscape Informed by<br>Extensive Experience, Stakeholder Engagement, and Market Research<br>• Global Advisory Boards with PAH Experts and PAH<br>Patients<br>• Interactions with Investigators, KOL’s, PAH<br>Treaters, Nurses, Patients, Advocacy Associations*<br>• Robust Market Research<br>– 100+ U.S. Physician Market Landscape Research<br>(Oct 2021)<br>– 100+ European Physician Market Landscape<br>Research (June 2022)<br>– 150+ U.S. Physician Conjoint Demand Study post<br>Sotatercept Data (Aug 2023)<br>*Individual interactions focus solely on treatment landscape unless<br>seeking bona-fide advice with an appropriate consulting agreement<br>23<br>Prof. Vizza MD investigator discussion |
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| PAH Treatment Pathways Have Not Changed Since 2005<br>and Outcomes Remain Poor<br>Epoprostenol Treprostinil Bosentan Ambrisentan Sildenafil Tadalafil<br>Prostacyclin Pathway Endothelin Pathway Nitric Oxide Pathway<br>61%-65% 5 Year Survival among Newly Diagnosed and Prevalent Patients<br>Multiple Agents Within Pathways<br>More Convenient Prostacyclin Pathway Routes of Administration<br>Infusion Inhalation Oral<br>More Aggressive Treatment Approaches<br>Initial Monotherapy Upfront Combination Therapy Treat to Low Risk<br>Significant Efforts to Optimize Traditional Pathways<br>24 24 |
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| Unmet Need Beyond Sotatercept<br>The STELLAR trial represents significant progress in therapy<br>for PAH however…<br>• 60% of patients did not meet multi-component<br>improvement measure<br>• 60% of patients did not achieve low risk on the simplified<br>French risk model<br>• 70% of patients did not improve functional class<br>• Long term effects not fully established<br>25 |
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| 80% of Physicians Would Prescribe an “IMPRES” Like<br>Inhaled TKI if it Were Available Alongside Sotatercept<br>80%<br>89%<br>57%<br>0%<br>20%<br>40%<br>60%<br>80%<br>100%<br>IMPRES Like Inhaled<br>TKI<br>STELLAR Like<br>Activin Signaling<br>Inhibitor<br>TORREY Like<br>Inhaled TKI<br>Market Research with >150 U.S. PAH Treating Physicians Conducted Post STELLAR Data*<br>% Who Would Prescribe Each Hypothetical Agent to Their Patients<br>26 *Proprietary Market Research with U.S. PAH Treating Physicians; Aug 2023. Data<br>based on product allocation exercise assuming all hypothetical agents were available |
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| AV-101: Unmet Need, Blockbuster Potential<br>27<br>Positioning<br>Added to 2 agents before<br>prostacyclin<br>Added to 3 agents before<br>parenteral prostacyclin<br>~ 35,000<br>Patients are treated<br>for PAH in the US<br>We estimate to be<br>taking 2-3 drugs<br>~65%<br>(~22,750) |
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| Positive Initial Regulatory Interactions and Feedback<br>Regulatory Interactions Completed<br>• FDA Pre-IND meeting in January 2020<br>• FDA and EMA Orphan Designation granted for AV-101 for the treatment of PAH<br>• Received EMA Scientific Advice in March 2021<br>• End-of-Phase-1 Meeting with FDA in April 2021<br>Feedback from FDA and EMA on Clinical Development<br>• A single Phase 2b/3 trial could support NDA<br>• Aligned on Phase 2b/3 endpoints for potential NDA/MAA submission<br>28 |
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| Intellectual Property Protection for AV-101 to 2040+<br>Multiple issued US patents covering AV-101 drug product and methods of use<br>• Patent coverage extends at least until 2040<br>• Current US patents being extended worldwide<br>Multiple additional pending applications pursuing<br>• Methods of manufacture<br>• Filing on other aerosol compositions<br>• Filing on mechanism of action (composition agnostic)<br>Regular reviews enacted to extend or file new IP based on discoveries in research,<br>clinical trials and CMC<br>29 |
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| Chemistry, Manufacturing and Controls<br>Stability of AV-101<br>• Release and stability testing supports<br>– API stability of at least 36 months<br>– Drug product stability of at least 30 months<br>• Filled product stability testing ongoing<br>30<br>Proprietary Methods<br>Several bulk<br>supplier options<br>Contracted manufacturing<br>and filling in place<br>Contracted with<br>supplier<br>AV-101 manufacturing and supply chain<br>GMP Imatinib<br>Mesylate<br>Processed to novel dry powder<br>formulation and capsules filled<br>Co-packaged<br>with device |
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| 31<br>AV-101 Device and Delivery Performance<br>AV-101 Device<br>• Off-the-shelf commercial scale dry powder inhaler<br>– No batteries, compressors or cords<br>– No sterile vials containing solutions or suspensions<br>– CE mark in EU and Device Master File registered with FDA<br>• Designed for ease of use and convenience<br>• Intended dosing of 2 capsules twice a day<br>• Replaced weekly<br>AV-101 Delivery Performance<br>• Consistently high delivered and fine particle dose<br>• Ideal size and size distribution for lung penetration<br>NOTE: Device planned for Phase 2b/3 trial was not used in Phase 1 trial, but delivery performance has been assessed. |
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| Significant Unmet<br>Need<br>Despite three drug<br>classes approved,<br>5-year survival for<br>newly diagnosed PAH<br>patients is 61%<br>Demonstrated<br>Clinical Benefit<br>The molecule in AV-101, imatinib, already<br>has shown clinical<br>benefit in a Phase 3<br>clinical trial<br>conducted by<br>Novartis of oral<br>imatinib mesylate in<br>PAH patients on top<br>of two or more<br>standard of care<br>therapies.<br>Unfortunately, AEs<br>with oral imatinib<br>were common and<br>development was<br>discontinued<br>Efficient Execution<br>FDA and EMA orphan<br>designation for AV-101<br>for the treatment of<br>PAH<br>Phase 1 SAD/MAD in<br>healthy volunteers<br>complete<br>Phase 2b dose-ranging<br>portion of a Phase 2b/3<br>trial in PAH patients.<br>Ph2b portion fully<br>enrolled with Ph2b data<br>expected in June 2024<br>Established Market<br>$6B+ market, yet<br>outcomes are poor<br>Aerovate: An Inventive Way Forward in PAH<br>32<br>Inventive<br>Solution<br>Anti-proliferative<br>targeted inhaled dry<br>powder PAH product<br>candidate AV-101<br>designed to provide<br>robust clinical benefit<br>of imatinib without<br>systemic AEs<br>observed with oral<br>imatinib |
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| 3333<br>Thank you! |
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