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): June 17, 2020

 

Millendo Therapeutics, Inc.

(Exact name of registrant as specified in its charter)

 

Delaware   001-35890   45-1472564
(State or other jurisdiction
of incorporation or organization)
  (Commission
File Number)
  (IRS Employer
Identification No.)

 

110 Miller Avenue, Suite 100
Ann Arbor, Michigan
  48104
(Address of principal executive offices)   (Zip Code)

 

Registrant’s telephone number, including area code: (734) 845-9000

 

(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 (see General Instruction A.2. below):

 

¨            Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨            Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

¨            Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

¨            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:

  

Title of each class   Trading
Symbol(s)
  Name of each exchange
on which registered
Common Stock, par value $0.001 per share   MLND   The Nasdaq Capital Market, LLC

 

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 5.02.Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensation Arrangements of Certain Officers.

 

On June 17, 2020, the Compensation Committee (the “Committee”) of the Board of Directors (the “Board”) of Millendo Therapeutics, Inc. (the “Company”) approved amendments to the Millendo Therapeutics, Inc. (formerly OvaScience, Inc.) 2012 Stock Incentive Plan (the “2012 Plan Amendment”) and the Millendo Therapeutics, Inc. 2019 Equity Incentive Plan (the “2019 Plan Amendment”, and together with the 2012 Plan Amendment, the “Plan Amendments”). The Plan Amendments, effective June 17, 2020, amend the Company’s 2012 Stock Incentive Plan and 2019 Equity Incentive Plan (together, as amended, the “Plans”). The Plans are designed to promote the interests of the Company and its stockholders by enabling the Company to offer an opportunity to employees and consultants to receive grants of equity-based and cash-based incentive awards, so as to better attract, retain, and reward them, to align their interests with those of stockholders, and to provide them with an incentive for outstanding performance to generate superior returns to the Company’s stockholders. The Plan Amendments require the acceleration of all outstanding unvested stock awards prior to the consummation of a change in control of the Company, if such stock awards are not assumed by the surviving corporation or acquiring corporation (or its parent company) or substituted with similar awards for such outstanding stock awards. The Plan Amendments affect the terms applicable to awards granted under, or otherwise subject to the terms of, the Plans, enabling the Company to continue to use the Plans as critical tools to attract, motivate, reward, and retain key employees.

 

The foregoing summary description of the Plan Amendments are qualified in their entirety by reference to the actual terms of the Plan Amendments, copies of which are attached to this Current Report on Form 8-K as Exhibits 10.1 and 10.2, and are incorporated by reference into this Item 5.02.

 

Item 5.07.Submission of Matters to a Vote of Security Holders.

 

At the annual meeting of the Company’s stockholders held on June 19, 2020, the Company’s stockholders voted on the following three proposals and the Company’s inspector of election certified the vote tabulations indicated below.

 

Proposal 1.   Election of Directors

 

The individuals listed below were elected as Class II directors at the Annual Meeting to serve on the Company’s board of directors for a term of three years or until their respective successors are duly elected and qualified.

 

Nominee  Votes For  Votes Withheld  Broker Non-Votes
Carole L. Nuechterlein, J.D.  10,352,756  92,990  3,179,760
James M. Hindman  10,366,960  78,786  3,179,760
Geoff Nichol, M.B., Ch.B., M.B.A.  10,404,975  40,771  3,179,760

 

Proposal 2.   Ratification of the Selection of the Company’s Accounting Firm

 

Proposal 2 was a proposal to ratify the appointment of Ernst & Young LLP as the Company’s independent registered public accounting firm for the year ending December 31, 2020. This proposal was approved with the votes set forth below:

 

Votes For  Votes Against  Abstentions
13,462,893  112,581  50,032

 

Proposal 3.   Approval of the Compensation of the Company’s Named Executive Officers

 

Proposal 3 was a proposal to approve the compensation of the Company’s named executive officers, on an advisory basis. This proposal was approved with the votes set forth below:

 

Votes For  Votes Against  Abstentions  Broker Non-Votes
8,812,189  1,132,009  501,548  3,179,760

 

 

 

 

Item 8.01Other Events.

 

On June 23, 2020, the Company issued a press release providing a corporate and pipeline update, and updated the Corporate Presentation that it intends to use in connection with its presentations at conferences and in meetings with investors. Copies of the Company’s press release and Corporate Presentation are attached as Exhibit 99.1 and Exhibit 99.2, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.

 

 

Item 9.01 Financial Statements and Exhibits.

 

(d)    Exhibits

 

Exhibit
No.
  Description
10.1+   Amendment to the Millendo Therapeutics, Inc. (formerly OvaScience, Inc.) 2012 Stock Incentive Plan
     
10.2+   Amendment to the Millendo Therapeutics, Inc. 2019 Equity Incentive Plan
     
99.1   Press Release of the Company, dated June 23, 2020
     
99.2   Corporate Presentation of the Company, dated June 23, 2020

 

+     Indicates management contract or compensatory plan.

 

 

 

 

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.

 

    MILLENDO THERAPEUTICS, INC.
     
Date: June 23, 2020 By: /s/ Julia C. Owens, Ph.D.
    Julia C. Owens, Ph.D.
    President and Chief Executive Officer

 

 

 

 

 

 

 

Exhibit 10.1

 

AMENDMENT TO

MILLENDO THERAPEUTICS, INC.

(formerly ovascience, inc)

2012 stock INCENTIVE plan

 

Whereas, the Board of Directors (the “Board”) of Millendo Therapeutics, Inc. (formerly OvaScience, Inc.) (the “Company”) previously approved and adopted the 2012 Stock Incentive Plan (the “Plan”);

 

Whereas, the Board has delegated authority to the Compensation Committee of the Board (the “Committee”) to administer the Plan;

 

Whereas, the Committee has determined that it is in the best interest of the Company to amend the Plan as set forth in this Amendment; and

 

Whereas, the Committee has the authority to amend the Plan pursuant to Section 11(d) of the Plan.

 

Now, Therefore, the Plan is hereby amended as follows:

 

1.                   Section 9(b)(2)(A) of the Plan is hereby amended to add the following to the end thereof:

 

Notwithstanding the foregoing, in the event of a Reorganization Event in which outstanding Awards are not assumed pursuant to Section 9(b)(2)(A)(i), then the vesting and exercisability of any Awards that are subject to time-based vesting requirements will be accelerated in full to a date prior to the effective time of such Reorganization Event (contingent upon the effectiveness of the Reorganization Event) as the Board determines (or, if the Board does not determine such a date, to the date that is 15 days prior to the effective time of the Reorganization Event). If an Award becomes fully vested and exercisable in lieu of assumption or substitution in the Reorganization Event, the Board shall notify the impacted Participants in writing or electronically thereof, and Awards shall terminate if not exercised (if applicable) at the effective time of the Reorganization Event (contingent upon the effectiveness of the Reorganization Event).”

 

2.                   All other terms and conditions of the Plan shall remain in full force and effect.

 

3.                   Capitalized terms used herein and not otherwise defined herein shall have the meanings set forth in the Plan.

 

I hereby certify that the foregoing Amendment to the Plan was duly adopted by the Compensation Committee of the Board of Directors of the Company as of June 17, 2020.

  

   
  /s/ Tamara Joseph
  Tamara Joseph
  General Counsel

 

 

 

 

Exhibit 10.2

 

AMENDMENT TO

MILLENDO THERAPEUTICS, INC.

2019 EQUITY INCENTIVE plan

 

Whereas, the Board of Directors (the “Board”) of Millendo Therapeutics, Inc. (the “Company”) previously approved and adopted the 2019 Equity Incentive Plan (the “Plan”);

 

Whereas, the Board has delegated authority to the Compensation Committee of the Board (the “Committee”) to administer the Plan;

 

Whereas, the Committee has determined that it is in the best interest of the Company to amend the Plan as set forth in this Amendment; and

 

Whereas, the Committee has the authority to amend the Plan pursuant to Section 2(b)(vi) of the Plan.

 

Now, Therefore, the Plan is hereby amended as follows:

 

1.                   Section 9(c) of the Plan is hereby amended to add the following paragraph to the end thereof:

 

Notwithstanding the foregoing, if the surviving corporation or acquiring corporation (or its parent company) does not assume or continue outstanding Stock Awards or substitute similar awards for such outstanding Stock Awards, then the vesting and exercisability of any Stock Awards that are subject to time-based vesting requirements will be accelerated in full to a date prior to the effective time of such Transaction (contingent upon the effectiveness of the Transaction) as the Board determines (or, if the Board does not determine such a date, to the date that is 15 days prior to the effective time of the Transaction). If a Stock Award becomes fully vested and exercisable in lieu of assumption or substitution in the Transaction, the Board shall notify the impacted Participants in writing or electronically thereof, and the Stock Award shall terminate if not exercised (if applicable) at the effective time of the Transaction (contingent upon the effectiveness of the Transaction).”

 

2.                   All other terms and conditions of the Plan shall remain in full force and effect.

 

3.                   Capitalized terms used herein and not otherwise defined herein shall have the meanings set forth in the Plan.

 

I hereby certify that the foregoing Amendment to the Plan was duly adopted by the Compensation Committee of the Board of Directors of the Company as of June 17, 2020.

 

  /s/ Tamara Joseph
  Tamara Joseph
  General Counsel

 

 

 

 

 

 

Exhibit 99.1

 

 

Millendo Therapeutics Provides Corporate and Pipeline Update

 

– MLE-301, a selective neurokinin 3 receptor (NK3R) antagonist, advancing with first-in-human trials expected to initiate in 3Q20 –

 

– Further investment in nevanimibe for congenital adrenal hyperplasia (CAH) not planned following interim data review –

 

– Strategic evaluation in place to determine future corporate strategy –

 

ANN ARBOR, Mich., June 23, 2020 Millendo Therapeutics, Inc. (Nasdaq: MLND), a biopharmaceutical company primarily focused on developing novel treatments for endocrine diseases with significant unmet needs, announced today that it has taken steps forward in its evaluation of strategic options to determine the company’s future direction. As part of these efforts, Millendo has engaged SVB Leerink to support the strategic review process. The company finished Q1 2020 with $58.9 million in cash, cash equivalents and restricted cash.

 

“Our board of directors and leadership team recognize the importance of conducting a comprehensive and strategic review. We are aligned in our focus on evaluating our pipeline and its potential, beginning with the advancement of MLE-301,” said Julia C. Owens, President and Chief Executive Officer of Millendo Therapeutics. “Our objective is to come away from this process with an actionable plan that leverages our assets, capital and capabilities in a way that maximizes shareholder value.”

 

MLE-301, a selective neurokinin 3 receptor (NK3R) antagonist, continues to advance to first-in-human trials: An IND has been filed to study MLE-301 for the treatment of vasomotor symptoms (VMS), also known as hot flashes and night sweats, in menopausal women. VMS currently impact 70% of peri/post-menopausal women, representing over 20 million women in the US. Phase 1 clinical studies are expected to initiate in 3Q20.

 

Interim review of nevanimibe open-label Phase 2b study in CAH completed: Results from 10 subjects, nine from cohort 1 and one from cohort 2, with at least 12 weeks of treatment with nevanimibe in this open-label, continuous dose escalation study showed that one patient (10%) met the primary endpoint of achieving 17- hydroxyprogesterone (17-OHP) levels less than or equal to 2-times the upper limit of normal (ULN). Treatment under the amended protocol with dose titration starting at 500 mg BID improved tolerability of nevanimibe. However, based on the observed level of nevanimibe activity and the changing competitive environment, no further investment in the program is currently planned.

 

 

 

 

About MLE-301
MLE-301 is a neurokinin 3 receptor (NK3R) antagonist that is being developed as a potential treatment of vasomotor symptoms (VMS), commonly known as hot flashes and night sweats, in menopausal women. NK3R plays a key role in regulating the activity of KNDy (kisspeptin/NKB/dynorphin) neurons, which are believed to participate in the generation of VMS. By inhibiting the NK3R signaling on the KNDy neurons and potentially other NK3R-expressing neurons that propagate heat dissipation signals through the hypothalamus, MLE-301 aims to reduce the effects of hyperactive KNDy neurons and thereby address vasomotor symptoms.

 

About Nevanimibe

Nevanimibe decreases adrenal steroidogenesis through the inhibition of acyl coenzyme A: cholesterol acyltransferase 1, or ACAT1, and is being studied for the treatment of classic congenital adrenal hyperplasia (CAH). CAH is a rare, monogenic adrenal disease that requires lifelong treatment with exogenous cortisol, often at high doses. These chronic high doses of cortisol can result in side effects that include diabetes, obesity, hypertension and psychological problems. An interim review of data from the Phase 2b trial of nevanimibe in CAH (NCT03669549) was conducted; results from 10 subjects with at least 12 weeks of treatment with nevanimibe in the open-label, continuous dose escalation study showed that one patient (10%) met the primary endpoint of achieving 17-hydroxyprogesterone (17-OHP) levels less than or equal to 2-times the upper limit of normal (ULN).

 

About Millendo Therapeutics, Inc.
Millendo Therapeutics is a biopharmaceutical company primarily focused on developing novel treatments for endocrine diseases where current therapies do not exist or are insufficient. Millendo seeks to create distinct and transformative treatments where there is a significant unmet medical need. The company is currently advancing MLE-301 for the treatment of vasomotor symptoms associated with menopause. For more information, please visit www.millendo.com.

 

Cautionary Statement Regarding Forward-Looking Statements

Certain statements contained in this press release regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, you can identify forward-looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. These include statements with respect Millendo’s strategic review and results thereof, Millendo’s financial condition, Millendo’s future capital needs, the impact of Millendo’s plan to not further invest in the nevanimibe program, Millendo’s timeline for the continued development of MLE-301 for menopausal vasomotor symptoms, and, therefore, you are cautioned not to place undue reliance on them. Such forward-looking statements are based on Millendo’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including that Millendo has incurred significant losses since inception, Millendo has a limited operating history and has never generated any revenue from product sales, Millendo will require additional capital to finance its operations, Millendo's future success is dependent on the successful clinical development, regulatory approval and subsequent commercialization of current and any future product candidates, preclinical studies or earlier clinical trials are not necessarily predictive of future results and the results of Millendo's clinical trials may not support Millendo's product candidate claims, Millendo may encounter substantial delays in its clinical trials or Millendo may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities, enrollment and retention of patients in clinical trials is an expensive and time-consuming process and could be made more difficult or rendered impossible by multiple factors outside Millendo's control, Millendo's product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, or limit their commercial potential, Millendo faces substantial competition and Millendo’s business, preclinical studies and clinical development programs and timelines, its financial condition and results of operations could be materially and adversely affected by the current COVID-19 pandemic. You should refer to the risk factor disclosure set forth in the periodic reports and other documents Millendo files with the Securities and Exchange Commission available at www.sec.gov, including without limitation Millendo’s Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2020.

 

New factors emerge from time to time and it is not possible for Millendo to predict all such factors, nor can Millendo assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this press release are based on information available to Millendo as of the date of this press release. Millendo disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law.

 

 

 

 

Millendo Investor Contact:
Connie Chang

Millendo Therapeutics
734-864-8006
chang@millendo.com
 
Millendo Media Contact:
Julie Bane
MacDougall
617-821-1089
jbane@macbiocom.com

###

  

 

 

 

 

 

 

Exhibit 99.2

 

 

Corporate Presentation June 2020

 

 

 

Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this presentation regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, you can identify forward-looking statements by the words “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue” and “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. These include statements with respect to Millendo’s strategic review and results thereof, Millendo’s financial condition, Millendo’s future capital needs, the impact of Millendo’s plan to not further invest in the nevanimibe program, Millendo’s timeline for the continued development of MLE-301 for menopausal vasomotor symptoms, and, therefore, you are cautioned not to place undue reliance on them. Such forward-looking statements are based on Millendo’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including that Millendo has incurred significant losses since inception, Millendo has a limited operating history and has never generated any revenue from product sales, Millendo will require additional capital to finance its operations, Millendo's future success is dependent on the successful clinical development, regulatory approval and subsequent commercialization of current and any future product candidates, preclinical studies or earlier clinical trials are not necessarily predictive of future results and the results of Millendo's clinical trials may not support Millendo's product candidate claims, Millendo may encounter substantial delays in its clinical trials or Millendo may fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities, enrollment and retention of patients in clinical trials is an expensive and time-consuming process and could be made more difficult or rendered impossible by multiple factors outside Millendo's control, Millendo's product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, or limit their commercial potential, Millendo faces substantial competition and Millendo’s business, preclinical studies and clinical development programs and timelines, its financial condition and results of operations could be materially and adversely affected by the current COVID-19 pandemic. You should refer to the risk factor disclosure set forth in the periodic reports and other documents Millendo files with the Securities and Exchange Commission available at www.sec.gov, including without limitation Millendo’s Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2020. New factors emerge from time to time and it is not possible for Millendo to predict all such factors, nor can Millendo assess the impact of each such factor on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements included in this presentation are based on information available to Millendo as of the date hereof. Millendo disclaims any obligation to update such forward-looking statements to reflect events or circumstances after the date of this press release, except as required by applicable law. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and Millendo's own internal estimates and research. While Millendo believes these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of Millendo's internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. 2

 

 

 

Millendo Therapeutics (Nasdaq: MLND) Strategic evaluation underway to reposition company for success Evaluating strategic options from position of financial strength with cash balance of $58.9M as of March 31, 2020* MLE-301, a novel NK3R antagonist for the treatment of menopausal vasomotor symptoms, expected to initiate first-in-human clinical studies in 3Q20 Seeking opportunities for potential pipeline expansion by leveraging our demonstrated experience in acquiring and in-licensing product candidates Experienced leadership team with deep development expertise to evaluate and execute on company strategy * Includes cash, cash equivalents and restricted cash 3

 

 

 

MLE-301 for Menopausal Vasomotor Symptoms

 

 

 

Vasomotor Symptom (VMS) Market is Significant Over 20 million women in the U.S. suffer from VMS associated with menopause MLE-301 • VMS are defined as hot flashes and night sweats and cause sensations of heat and/or perspiration Over 20M women are currently experiencing hot flashes in US – Median age of onset of 51 years old1 – Impacts up to 80% of postmenopausal women2 – Duration varies by stage of first VMS4 – Varies by BMI, ethnicity and smoking VMS impacts QoL, sleep, and mood3 • • 1. 2. 3. 4. Grady, 2006 NEJM Pinkerton, 2016 Menopause Joffe, 2011 Ob-Gyn Clin N. America Avis, JAMA Intern Med. 2015;175(4):531-539. 5 Median symptom duration of 7.4 years

 

 

 

The Market Is Looking to Break the Efficacy/Safety Trade-off Potential efficacy of estrogens without cancer and cardiovascular concerns MLE-301 • Estrogens demonstrate reduction in VMS frequency by ~80-90%, while SSRI efficacy is limited (~40-60%) – Estrogen replacement therapy was significant market, but plummeted upon Women’s Health Initiative (WHI) findings – WHI caused concerns of stroke, DVT and cancers resulting in black box warnings Efficacy • Women suffering from vasomotor symptoms want an effective non-hormonal option – Avoid concerns for cancer and CV risk – OTCs and SSRIs: insufficient hot flash control • NK3R antagonists including MLE-301 are positioned to potentially break the trade-off between efficacy and safety seen with estrogen therapy Safety 6 EstrogensMLE-301 SSRIs OTCs

 

 

 

NK3R is a Key Receptor on KNDy Neurons Overactive KNDy signaling in menopausal women is believed to lead to VMS MLE-301 • Estrogen is a negative regulator of KNDy neurons – Absence of estrogen-driven negative feedback following menopause causes KNDy neurons to become hypertrophic – Hyperactivity in KNDy neurons is believed to initiate the process that causes VMS – Inhibiting NK3R signaling seeks to restore normal functioning of heat dissipation effectors and to resolve the dysregulation KNDy neurons are overactive in menopausal women with VMS KNDy Neuron GnRH neuron ‘Heat dissipation’ neuron • KNDy neurons are implicated in the thermoregulatory pathway – NK3R antagonists can also impact Hypothalamic-Pituitary-Gonadal (HPG) axis Vasomotor Symptoms 7

 

 

 

NK3R is Implicated in Vasomotor Symptoms Administration of NKB induced VMS in 8/10 women MLE-301 • Robust genetic, pharmacodynamic, and clinical data support the role of NK3R in VMS NK3R Signaling Induces VMS in Women Human mutations in NK3R and its ligand NKB show defects in Hypothalamic-Pituitary-Gonadal (HPG) axis signaling Genomic studies have identified mutations associated with hot flashes in the NK3R gene locus Administration of NK3R ligand (NKB) results in hot flashes – – – 8

 

 

 

NK3R Antagonist Effects Are Comparable Clinical data has established class efficacy to Estrogen MLE-301 • Three different NK3R antagonists have been associated with reductions of hot flashes in clinical studies – MLE4901 (Millendo), NT-814 (KaNDy Therapeutics) and fezolinetant (Astellas) – Effects appear similar across the class, and similar to estrogen, but with more rapid onset of action •Reductions in hot flash frequency and severity observed by day 3 0 -20 -40 -60 • Elevated liver function tests (LFT) have been seen with two NK3R antagonist product candidates -80 Millendo terminated development of MLE4901 in 2017 due to LFT signal LFTs reported at higher doses of fezolinetant in Phase 2b study Unclear if LFTs are a class effect •NK3R not expressed in liver – – – -100 PlaceboNK3Ra Includes VMS clinical results for 3 different NK3R antagonists in orange (MLE4901 Phase 2a, fezolinetant Phase 2a and 2b, KaNDy’s NT-814 Phase 2a), and estrogen/HRT (blue) study. 9 % Change in HF Frequency from Baseline

 

 

 

MLE-301: NK3R Antagonism in Preclinical Studies MLE-301 • MLE-301 is a novel, potent, selective NK3R antagonist – Potential to demonstrate comparable vasomotor effects as other NK3R antagonist candidates – Over 25-45x as selective for NK3R vs NK1R/2R – As a chemically distinct molecule, MLE-301 is intended to avoid the LFT elevations seen with other NK3Rs • Preclinical data suggests MLE-301 engages target NK3R binding inhibition (IC50) is 25 nM >70% reduction in testosterone in canine study observed at higher doses •NK3R antagonism believed to impact both the HPG axis and the thermoregulatory pathway •Experience with MLE4901 suggests impacts are correlated – – 10

 

 

 

MLE-301 Pursuing Efficient Clinical De-risking Strategy Phase 1 intended to de-risk efficacy and Phase 2 to address LFT concerns MLE-301 (12-week study) 12-week HF severity substantially de-risk T = testosterone LH = luteinizing hormone HF = hot flashes 11 Accomplished Planned Preclinical SAD MAD (7-day study) Phase 2 Efficacy Objectives x Suppression of T in canines Suppression of LH / T in human males Reduction of HF frequency in post-menopausal women Reductions in 4-and frequency and LFT concerns x New chemical class Duration of dosing too short Duration and size sufficient to LFT concerns IND filed June 2020 Phase 1 studies starting 3Q 2020 2021-2022

 

 

 

Nevanimibe for Congenital Adrenal Hyperplasia (CAH)

 

 

 

Nevanimibe CAH Phase 2b Study Intrasubject, open-label dose escalation study with 16 weeks continuous dosing Nevanimibe • Study objectives: – Confirm Phase 2a proof of concept study demonstrating decrease in 17-hydroxyprogesterone nevanimibe treatment for 14 days – Determine adequate dose(s) to initiate registration program Study design: (17-OHP) with • Cohort 1: Patients with elevated androgen and 17-OHP levels 17-OHP ≥ 4x ULN baseline period Primary Endpoint N=20-24 (10-12 per cohort) Cohort 2: Patients on high glucocorticoid (GC) doses 17-OHP < 4x ULN GC down-titration/17-OHP stabilization baseline period 17-OHP < 2x ULN 10-12 sites 16 WEEKS OF CONTINUOUS NEVANIMIBE DOSING 500 mg BID, 1000 mg BID, 1500 mg BID, and 2000 mg BID ● Dose titration based on 17-OHP levels ClinicalTrials.gov Identifier: NCT03669549 Note: Study currently paused 13

 

 

 

Nevanimibe CAH Phase 2b: Interim Data Analysis Analyzed 10 subjects (9 cohort 1, 1 cohort 2) with at least 12 weeks of treatment Nevanimibe • Efficacy: – 50% of patients achieved a ≥ 50% decrease in 17-OHP, confirming nevanimibe activity in decreasing 17-OHP levels in patients with CAH – 1/10 (10%) of patients achieved the primary endpoint of reaching 17-OHP levels ≤ 2x upper limit of normal (ULN) – Decreases in 17-OHP did not consistently translate into decreases in androstenedione • Safety: – Starting dose of 500 mg BID was better tolerated than a 1000 mg BID starting dose – Adverse events reported were mostly gastrointestinal, skin and urinary events – Most adverse events were mild to moderate • Based on the observed level of nevanimibe activity and the changing competitive further investment in the nevanimibe program is currently planned environment, no 14

 

 

 

 

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