UNITED STATES
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FORM 8-K
CURRENT REPORT
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Item 8.01 Other Events.
On June 21, 2023, Lumos Pharma, Inc. issued a press release titled "Lumos to Highlight New LUM-201 Data and Analysis Presented at ENDO 2023 in Virtual KOL Webinar."
A copy of the press release and the presentation materials are attached hereto as Exhibit 99.1 and 99.2, respectively, and are incorporated herein by reference.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit Number | Description | |||||||
| 99.1 | Press Release, dated June 21, 2023, entitled "Lumos to Highlight New LUM-201 Data and Analysis Presented at ENDO 2023 in Virtual KOL Webinar." | |||||||
| 99.2 | ||||||||
SIGNATURES
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.
Dated: June 21, 2023
| LUMOS PHARMA, INC., a Delaware corporation | |||||
| By: | /s/ Richard J. Hawkins | ||||
| Richard J. Hawkins | |||||
| Its: | Chief Executive Officer | ||||
Lumos to Highlight New LUM-201 Data and Analysis Presented
at ENDO 2023 in Virtual KOL Webinar
Webinar to Review Data Demonstrating
Potential Drug Effect and Durable Response
Webinar to be held Today June 21, 2023 at 11:00 AM Eastern Time
AUSTIN, TX, June 21, 2023 – Lumos Pharma, Inc. (NASDAQ:LUMO), a biopharmaceutical company advancing an oral therapeutic candidate for idiopathic Pediatric Growth Hormone Deficiency (iPGHD) through Phase 2 clinical trials, is hosting today a virtual Key Opinion Leader (KOL) Webinar where Drs. Fernando Cassorla and Michael Tansey will highlight the encouraging new data and analysis on oral LUM-201 for idiopathic PGHD from the Phase 2 PK/PD OraGrowtH212 and dose-finding OraGrowtH210 Trials presented at the Endocrine Society (ENDO) Annual Meeting, held in Chicago, Illinois, June 15-18, 2023.
The event will feature presentations by KOLs in the field of pediatric endocrinology, Fernando Cassorla, MD, Chief of Pediatric Endocrinology, University of Chile, and Michael Tansey, MD, Clinical Professor of Pediatrics-Endocrinology and Diabetes, University of Iowa, Carver College of Medicine, who will review interim data from our Phase 2 OraGrowtH210 and OraGrowtH212 Trials presented at ENDO. Drs. Cassorla and Tansey will be available to answer questions following their formal presentations. To register for the virtual KOL Event, please click through the link HERE.
Drs. Cassorla and Tansey gave two oral presentations in the Update on Growth Disorders session at the 2023 ENDO Meeting. Presentation slides will be available from the Events and Presentations section of the Lumos website.
Dose Responsiveness of LUM-201 as Measured by Acute GH Response and IGF-1 and Annualized Height Velocity (AHV) Measured at 6 Months in the Interim Analysis of the OraGrowtH212 Study in Idiopathic Pediatric Growth Hormone Deficiency (iPGHD) (Fernando Cassorla, MD, Chief of Pediatric Endocrinology, University of Chile)
•New data from OraGrowtH212 trial shows durable response after 12 months of LUM-201 administration
•Clear evidence of potential drug effect observed in consistent improvement in average height velocity over baseline
•Treatment with LUM-201 increased serum IGF-1 concentration and SDS values, which remained within normal range while contributing to meaningful increases in height velocity
•Data support physiologic mechanism of action of LUM-201
Growth Response of Oral LUM-201 in OraGrowtH210 and OraGrowtH212 Trials in Idiopathic Pediatric Growth Hormone Deficiency (iPGHD): Combined Analysis Interim Analysis Data (Michael Tansey, MD, Clinical Professor of Pediatrics-Endocrinology and Diabetes, University of Iowa)
•Dr. Tansey presented new analysis of combined interim data from two Phase 2 trials at the 1.6 mg/kg/day and 3.2 mg/kg/day doses, including 15 subjects from the OraGrowtH212 Trial and 20 subjects from the OraGrowtH210 Trial
•Results of the analysis of the additional OraGrowtH212 subjects combined with OraGrowtH210 subjects continue to demonstrate that there is a durable response to LUM-201 from 6 to 12 months
•Pre-treatment baseline AHV data, which was not captured for all of the subjects in our database, was available for 31 of the 35 subjects and showed that LUM-201 at both the 1.6 mg/kg/day and 3.2 mg/kg/day produced clinically meaningful increase in AHV from baseline
•No treatment related Serious Adverse Events (SAEs), no discontinuation due to AEs, and no meaningful safety signals observed
KOL Biographies
Fernando Cassorla, M.D. is currently Chief of Pediatric Endocrinology at the Institute of Maternal and Child Research of the University of Chile, a position he has held since 1993. Previously, beginning in 1979 Dr. Cassorla served as Senior Investigator at the Developmental Endocrinology Branch of the National Institute of Child Health and Human Development, rising to the position of Clinical Director of this Institute in 1990. He has authored numerous chapters in pediatric endocrinology, authored or co-authored over 200 original articles in peer reviewed journals, and has presented over 300 abstracts at scientific meetings. Dr. Cassorla received his MD from the University of Chile. He is Board Certified in both Pediatrics and Pediatric Endocrinology, having completed his pediatric residency at the Albany Medical Center in New York and his fellowship in Pediatric Endocrinology at the Children´s Hospital of Philadelphia. Dr. Cassorla has received several international awards for his work and was elected to the Chilean Academy of Medicine for a lifetime position in 2003.
Michael Tansey, M.D. is currently Clinical Professor, Department of Pediatrics, Division of Pediatric Endocrinology and Diabetes, University of Iowa, Iowa City, Iowa, a position he has held since 2012, having first served as Clinical Assistant Professor there 2001-2006, then as Clinical Associate Professor 2006-2012. Dr. Tansey also currently serves as Clinical Director for Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Iowa. He has been a co-investigator for one of the 5 clinical centers for the NIH funded Diabetes Research in Children Network “DirecNet” group since 2001 and has co-authored numerous peer-reviewed scientific publications on brain function and growth in children with Type 1 diabetes. Dr. Tansey received his MD from Loyola Stritch School of Medicine, Maywood, Illinois, and completed his residency in pediatrics and his fellowship in pediatric endocrinology at the University of Iowa Children’s Hospital and University of Iowa Hospitals and Clinics, respectively. He has received several awards including the Riesz Award, University of Iowa, and the Mary Tyler Moore and S. Robert Levine, MD, Excellence in Clinical Research Award.
About Pediatric Growth Hormone Deficiency and LUM-201
Pediatric Growth Hormone (GH) Deficiency is the consequence of inadequate secretion of growth hormone from the pituitary gland in children resulting in low GH in the body, insufficient production of downstream signaling molecules required for growth, and the subsequent lack of growth. LUM-201, also known as ibutamoren, is an orally administered investigational small molecule that promotes the secretion of GH from the pituitary gland and represents an opportunity for moderate idiopathic PGHD patients – the majority of the total PGHD population1 – to
avoid the daily or weekly injections involved with current or forthcoming therapies. LUM-201 has been observed to increase the amplitude of endogenous pulsatile GH secretion, which mimics the natural pattern of GH secretion.
1 Blum et al JES 2021
About Lumos Pharma
Lumos Pharma, Inc. is a clinical stage biopharmaceutical company focused on the development and commercialization of therapeutics for rare diseases. Lumos Pharma was founded and is led by a management team with longstanding experience in rare disease drug development. Lumos Pharma’s lead therapeutic candidate is LUM-201, an oral growth hormone stimulating small molecule, currently being evaluated in several Phase 2 clinical trials for the treatment of idiopathic Pediatric Growth Hormone Deficiency (iPGHD): the dose-finding OraGrowtH210 Trial; the PK/PD mechanistic OraGrowtH212 Trial; and a switch trial, the OraGrowtH213 Trial. If approved by the FDA, LUM-201 would provide an orally administered alternative to recombinant growth hormone injections that PGHD subjects otherwise endure for many years of treatment. LUM-201 has received Orphan Drug Designation in both the US and EU. For more information, please visit https://lumos-pharma.com/.
###
Investor & Media Contact:
Lisa Miller
Lumos Pharma Investor Relations
512-792-5454
ir@lumos-pharma.com
1 KOL Event Response to LUM-201 in Moderate PGHD Fernando Cassorla, MD and Michael Tansey, MD June 21, 2023
2 Forward Looking Statements This presentation contains proprietary and confidential information of Lumos Pharma, Inc. (“Lumos,” “we,” “us” and “our”), and such content should be considered “Confidential Information” and covered by your confidentiality obligations to Lumos. This presentation is made solely for informational purposes, and no representation or warranty, express or implied, is made by Lumos or any of its representatives as to the information contained in these materials or disclosed during any related presentations or discussions. This presentation contains forward-looking statements of Lumos that involve substantial risks and uncertainties. All such statements contained in this presentation are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We are passionate about our business, including LUM-201 and the potential it may have to help patients in the clinic. This passion feeds our optimism that our efforts will be successful and bring about therapeutics that are safe, efficacious, and offer a meaningful change for patients. Please keep in mind that actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. We have attempted to identify forward-looking statements by using words such as “projected,” "upcoming," "will," “would,” "plan," “intend,” "anticipate," "approximate," "expect," “potential,” “imminent,” and similar references to future periods or the negative of these terms. Not all forward-looking statements contain these identifying words. Examples of forward-looking statements include, among others, statements we make regarding progress in our clinical efforts including comments concerning screening and enrollment for our trials, momentum building in our LUM-201 program for PGHD, anticipated timing of interim analyses of trials, LUM-201’s therapeutic potential when administered to pediatric subjects with idiopathic or moderate growth hormone deficiency, that the interim sample size should be adequate to provide an initial indication of LUM 201’s impact, expecting the primary outcome data readout for our trials, market size potential for LUM-201, predictions regarding LUM-201, goals with respect to LUM-201, the potential to expand our LUM-201 platform into other indications, future financial performance, results of operations, cash position, cash use rate and sufficiency of our cash resources to fund our operating requirements through the primary outcome data readout from the OraGrowtH210 and OraGrowtH212 Trials, and any other statements other than statements of historical fact. We wish we were able to predict the future with 100% accuracy, but that just is not possible. Our forward-looking statements are neither historical facts nor assurances of future performance. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make due to a number of important factors, including potential material differences between the interim results of our LUM-201 trials and the final results of the trials which are not known at this time, the effects of pandemics (including COVID-19), other widespread health problems, the Ukraine-Russia conflict, the outcome of our future interactions with regulatory authorities, our ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the ability to obtain the necessary patient enrollment for our product candidate in a timely manner, the ability to successfully develop our product candidate, the timing and ability of Lumos to raise additional equity capital as needed and other risks that could cause actual results to differ materially from those matters expressed in or implied by such forward-looking statements. You should not rely on any of these forward-looking statements and, to help you make your own risk determinations, we have provided an extensive discussion of risks that could cause actual results to differ materially from our forward-looking statements in the "Risk Factors" section and elsewhere in our Annual Report on Form 10-K for the year ended December 31, 2022, as well as other reports filed with the SEC including our Quarterly Reports on Form 10-Q filed after such Annual Report. All of these documents are available on our website. Before making any decisions concerning our stock, you should read and understand those documents. We anticipate that subsequent events and developments will cause our views to change. We may choose to update these forward-looking statements at some point in the future; however, we disclaim any obligation to do so. As a result, you should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation. The data contained herein is derived from various internal and external sources. All of the market data in the presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Further, no representation is made as to the reasonableness of the assumptions made within or the accuracy or completeness of any projections or modeling or any other information contained herein. Any data on past performance or modeling contained herein is not an indication as to future performance. 5.3.2023
3 Agenda • Rick Hawkins, Chief Executive Officer & Chairman • John McKew, PhD, President & Chief Scientific Officer • Michael Tansey, MD, University of Iowa • Fernando Cassorla, MD, University of Chile
4 Key Opinion Leaders in the Field of Pediatric Endocrinology Michael Tansey, MD is currently Clinical Professor, Dept. of Pediatrics, Division of Pediatric Endocrinology and Diabetes, University of Iowa, Iowa City, a position he has held since 2012, having first served as Clinical Assistant Professor 2001-2006, then as Clinical Associate Professor 2006-2012. Dr. Tansey also serves as Clinical Director for Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Iowa. He has been a co-investigator for one of 5 clinical centers for the NIH-funded Diabetes Research in Children Network “DirecNet” group since 2001 and has co-authored numerous peer- reviewed scientific publications on brain function and growth in children with Type 1 diabetes. Dr. Tansey received his MD from Loyola Stritch School of Medicine, Maywood, Illinois, and completed his residency in Pediatrics at the University of Iowa Children’s Hospital and his fellowship in Pediatric Endocrinology at the University of Iowa Hospitals and Clinics. He has received several awards including the Riesz Award, University of Iowa, and the Mary Tyler Moore and S. Robert Levine, MD, Excellence in Clinical Research Award. Fernando Cassorla, MD is currently Chief of Pediatric Endocrinology at the Institute of Maternal and Child Research of the University of Chile, a position he has held since 1993. Previously, Dr. Cassorla served as Senior Investigator at the Developmental Endocrinology Branch of the National Institute of Child Health and Human Development, rising to the position of Clinical Director of this Institute in 1990. He has authored numerous chapters in pediatric endocrinology, authored or co-authored over 200 original articles in peer reviewed journals, and has presented over 300 abstracts at scientific meetings. Dr. Cassorla received his MD from the University of Chile. He is Board Certified in both Pediatrics and Pediatric Endocrinology, having completed his residency in Pediatrics at the Albany Medical Center in New York and his fellowship in Pediatric Endocrinology at the Children´s Hospital of Philadelphia. Dr. Cassorla has received several international awards for his work including the European Society of Pediatric Endocrinology (ESPE) International Research Award, September 2022, and was elected to the Chilean Academy of Medicine for a lifetime position in 2003.
5 Overview Lead asset targeting children with growth disorders Novel Oral Rare Disease Asset Pipeline in a Product Solid Financial Position • Novel oral therapeutic asset, LUM-201, for growth hormone deficiency (GHD) disorders • LUM-201 acts within natural endocrine pathway, differentiated from injectable therapies • Worldwide injectable market for GHD disorders is $3.4 billion, excluding China* • Market for initial oral LUM-201 indication, Pediatric GHD (PGHD), is $1.2 billion* • Cash balance of $58.0 million as of close of 1Q 2023 • Cash runway into 3Q 2024, beyond Phase 2 OraGrowtH Trials primary outcome data Late-stage Trials in PGHD • Primary outcome data for two Phase 2 OraGrowtH Trials expected 4Q 2023 • PEM strategy de-risks trials by identifying and enrolling likely LUM-201 responders** PGHD = Pediatric Growth Hormone Deficiency * USA, Germany, France, Italy, Spain, UK, Japan (Grandview Research, Growth Hormone Market Forecast, 2019) ** PEM (Predictive Enrichment Marker) strategy consists of screening for PEM+ PGHD patients = Baseline IGF-1 > 30 ng/ml & Peak stimulation GH ≥ 5 ng/ml from single oral dose of LUM-201
6 Phase 2 OraGrowtH Trials – Primary Outcome Data Due Q4 2023 • Dose-finding multi-site study • N = 82 PEM+ PGHD subjects randomized • 4 treatment arms o 0.8 mg/kg/day LUM-201 o 1.6 mg/kg/day LUM-201 o 3.2 mg/kg/day LUM-201 o Standard dose rhGH control arm • Primary outcome at 6 months on therapy • On treatment for 24 months • To determine optimal Phase 3 dose • Mechanistic single-site PK/PD study • N = 22 PEM+ PGHD subjects randomized • 2 treatment arms o 1.6 mg/kg/day LUM-201 o 3.2 mg/kg/day LUM-201 • Q10 minute GH sampling for 12 hours • Primary outcome at 6 months on therapy • On treatment up to near-adult height • To demonstrate pulsatile LUM-201 MOA Primary Outcome Readout: 6-month AHV for All Subjects Additional AHV Data for Subjects at 9, 12, and 18+ Months on Treatment **Phase 2 trials are NOT powered for efficacy** * PEM-positive (PEM+) PGHD patients = PGHD patients with baseline IGF-1 > 30 ng/ml & peak GH ≥ 5 ng/ml from single oral 0.8 mg/kg dose of LUM-201
7 Historical rhGH Data Set Expectations for Growth on Therapy in Moderate PGHD rhGH 0204 rhGH GeNeSIS1 rhGH iPGHD2 rhGH KIGS3 0 4 8 12 16 20 n=3075 8.58 n=100 8.30 n=433 8.29 n=11 8.80 A n n u a li z e d H e ig h t V e lo c it y ( c m /y r) • GeNeSIS1, iPGHD2, and KIGS3 datasets demonstrating AHV at 12 months on rhGH • Merck 0204 AHV from 6 months of rhGH • These trials set precedent for expected growth on rhGH in moderate idiopathic PGHD • Prediction for growth in OraGrowtH210 is AHV of ~8.3- 8.6 cm/yr on both LUM-201 and rhGH based on historical data Historical Datasets for Moderate PGHD Expected Growth in OraGrowtH210 Trial Sources: 1 Blum et al JES 2021, 2 Lechuga-Sancho et al JPEM 2009, 3 Ranke et al JCEM 2010, 4 Bright et al JES 2021. Historical AHVs at 6 & 12 months on Daily Injectable rhGH in Moderate PGHD 6mos 12mos 12mos 12mos
8 Interim OraGrowtH210 Data: LUM-201 Growth in Line with Historical Norms rhGH growth not in line with historical norms for moderate PGHD Sources: 1 Blum et al JES 2021, 2 Lechuga-Sancho et al JPEM 2009, 3 Ranke et al JCEM 2010, 4 Bright et al JES 2021. Historical AHVs at 6 or 12 mos on injectable rhGH in Moderate PGHD OraGrowtH210 Trial AHV at 6 months in Moderate PGHD mg/kg LUM-201 rhGH 0201 rhGH rhGH rhGH GeN.1 iPGHD2 KIGS3 0.8 1.6 3.2 8.3 cm/yr 0204 • LUM-201 1.6 mg/kg/day growth of 8.6 cm/yr in line with historical data • rhGH cohort grew faster than expected due to outliers • Cohort baseline differences contributed to growth variances1,3 • Converging baseline characteristics seen at full enrollment should lead to better AHV balance AHV disparities should narrow at full data readout OraGrowtH210 Trial Interim Results 6mos 12mos 12mos 12mos
9 OraGrowtH210 Trial Baseline Characteristics at 50% & 100% Enrollment LUM-201 1.6 mg Mean (SD) N=10 rhGH Mean (SD) N=10 LUM-201 1.6 mg Mean (SD) N=22 rhGH Mean (SD) N=20 Age (months) 99.3 (28.3) 90.3 (26.7) 95.2 (27.3) 91.4 (23.3) Height (cm) 114.6 (9.6) 111.6 (11.9) 113.0 (11.0) 112.3 (10.5) Height SDS -2.35 (0.62) -2.29 (0.43) -2.42 (0.68) -2.23 (0.41) IGF-1 SDS -1.17 (0.72) -1.37 (0.48) -1.40 (0.57) -1.39 (0.47) MPH (cm) 166.98 (7.15) 168.78 (8.85) 165.4 (7.4) 169.1 (8.26) MPH SDS∆ 1.76 (0.60) 1.76 (0.73) 1.69 (0.81) 1.91 (0.65) BA Delay (yrs) 1.9 (0.5) 1.8 (1.0) 1.8 (0.9) 1.9 (0.9) BMI SDS1 -0.35 (0.79) +0.31 (1.05) -0.27 (0.90) +0.01 (0.95) * Preliminary assessment 1 Yang, et al. Nature Sci Rep 2019, 9(1); 16181 SDS = Standard deviation score MPH = Mid-parental height (Child’s target height) MPH SDS delta = (MPH SDS) – (Height SDS) BA = Bone age BMI = Body mass index At 50% enrollment At 100% enrollment* Imbalance between LUM-201 & rhGH arms narrows at full enrollment, which we expect will diminish the rhGH outlier impact
10 Expectations for a Registrational Phase 3 Trial in Moderate PGHD Based on recent peer registrational trials in PGHD Projected Design for Phase 3 Trial Anticipated Endpoints for Phase 3 Trial • International multi-center trial • ~200 PEM-positive (PEM+) moderate idiopathic PGHD subjects* • Subjects randomized 2:1 daily oral LUM-201 vs daily injectable rhGH • Stratification by age and 2-3 other factors based on Phase 2 data • 12-month treatment period • Primary endpoint: AHV at 12 months on treatment • Non-inferiority AHV margin of ~2 cm between LUM-201 & rhGH arms at 12 months * PEM-positive (PEM+) PGHD patients = PGHD patients with baseline IGF-1 > 30 ng/ml & peak GH ≥ 5 ng/ml from single oral 0.8 mg/kg dose of LUM-201
ENDO 2023 – Session OR21-03 Dose Responsiveness of LUM-201 as Measured by Acute GH Response and IGF-1 and Annualized Height Velocity (AHV) Measured at 6 Months in the Interim Analysis of the OraGrowtH212 Study in Idiopathic Pediatric Growth Hormone Deficiency (iPGHD) 1University of Chile, Santiago, Chile 2Lumos Pharma, Austin, TX Cassorla F1, MD; Román R1, MD; Johnson M2, PhD; Smith C2, MS; Avila A1, RN; Iñiguez G1, PhD; Baier I1, MD; Said D1, RN; Karpf DB2, MD; McKew JC2, PhD; Thorner M2, MB BS, DSc 11
Dr. Cassorla is an investigator for clinical studies with LUM-201 at the University of Chile (Sponsor - Lumos Pharma, Inc.) and has previously acted as a consultant for Debiopharm, Pfizer, Merck, Novo Nordisk and Sandoz. LUM-201 is an investigational compound and is not approved for use by the FDA or any other regulatory agency. Some of the slides in this presentation are derived or copied from corporate presentations previously given by Lumos Pharma, Inc. These slides are used with permission. Disclosure 12
Oral LUM-201 is a growth hormone (GH) secretagogue • Acts as a durable agonist of GH Secretagogue Receptor (GHSR1a) to stimulate GH release1 • LUM-201 has been observed to increase the amplitude of endogenous, pulsatile GH secretion over 24 hours2,3 • Another differentiating feature vs rhGH is the natural negative feedback mechanisms, which limit the potential for hyperstimulation and excessive increases in IGF-1 • LUM-201 promotes pulsatile GH secretion in a selective PGHD Population Moderate Idiopathic PGHD - Axis Responsive 1. Howard 1996 Science 273:974-977 2. Nass 2008 Ann Intern Med 149:601-611 3. Chapman 1997 J Clin Endocrinol Metab 82:3455-3463 LUM-201 (ibutamoren) – Mechanism of Action 13
Phase 2- Pulsatility and PK/PD Study Design Naive Idiopathic PGHD Patients Screening Baseline 6 months Height Height IGF-1 IGF-1 q10m x 12h GH q10m 12h GH Standard GH stimulation tests Peak GH to single LUM-201 PEM dose n = 11 LUM-201-3.2mg/kg/day n = 11 LUM-201-1.6 mg/kg/day R Dosing to near Adult Height Study Information • Open-label study: N = 22 • PGHD subjects that are rhGH-treatment naïve • Inclusion: Height < 2 SD, delayed bone age, peak GH response to a clonidine stimulation test between 3 and 10 ng • Dosing to near-adult height • Single, specialized clinical site University of Chile, Santiago Primary Endpoints: • Assess LUM-201 effect on endogenous GH pulsatility and Annualized Height Velocity (AHV) • Evaluate PK/PD in children Goals: • Confirm prior PK/PD data in adults & subset of Merck 020 trial • Support future regulatory filings & commercialization 14
Questions 1. Does LUM-201 dose-dependently augment endogenous GH pulses in patients with Idiopathic Pediatric Growth Hormone Deficiency (iPGHD)? 2. Will increased amplitude of GH pulsatility and increase in IGF-1 within normal range improve height velocity? 3. Is the effect on AHV durable out to 12 months? 15
Baseline Demographics Subjects N=15 1.6 mg N=8 3.2 mg N=7 Mean (SD) Age (mos) 96.9 (11.9) 95.0 (22.7) Height (cm) 115.2 (4.57) 113.1(9.97) Height SDS -2.12 (0.29) -2.34 (0.45) IGF-1 SDS -1.1 (0.535) -0.8 (0.377) MPH (cm) 161.8 (6.98) 160.82 (5.73) MPH SDS Δ 0.73 (0.47) 0.81 (0.43) BA Delay (yrs) 1.50 (0.26) 1.83 (0.88) BMI (SDS) -0.18 (0.96) +0.48 (1.02) Male/Female% 63/37 71/29 Differences between the two groups: • Slight imbalance in age and gender • Slight imbalance in delta below MPH, BMI, and bone age delay KEY: SDS = Standard deviation score MPH = Mid-parental height (Child’s target height) MPH SDS Δ = MPH SDS-Ht SDS BA = Bone age BMI = Body mass index16
AHV Before and After 6 months of LUM-201 Treatment 17 6-month observations: • LUM-201 raised the AHV (growth rate) from baseline after 6 months on therapy for both the 1.6 mg/kg cohort (p = 0.0006) and the 3.2 mg/kg cohort (p < 0.0001) • No statistical difference exists between the two cohorts at each timepoint • As expected, greater growth response was observed in patients with lower baseline height velocity
Durable Response After 12 Months of LUM-201 Administration Mean AHV’s in OraGrowtH212 Trial 1Ranke, et.al. 2010 JCEM 95(3):1229-1237.18
First year Second year Severe PGHD Moderate PGHD Height Velocity During Daily rhGH Therapy Ranke, et.al. 2010 JCEM 95(3):122919
20 IGF-1 Values: Treatment with LUM-201 Increased Serum IGF-1 Concentration and IGF-1 SDS Values Conclusions : • There is a significant increase in IGF-1 levels that remains within the normal range • Based on the MOA of LUM-201, these data support the physiological IGF-1 feedback
IGF-1, GH Pulsatility, Height Velocity: Patient A 1.6 mg/kg/day 0 200 400 600 800 0 2 4 6 8 10 Patient A Time (min) S e ru m G ro w th H o rm o n e (n g /m l) 21 Patient A Baseline GH Baseline 6 months LUM-201 1.6 mg/kg/d IGF-1 (ng/ml) 179.3 Q10m 12h GH AUC0-12 (ng*hr/ml) 798.8 Height velocity (cm/yr) 5.6 Serum GH at Baseline
0 200 400 600 800 0 2 4 6 8 10 Patient A Time (min) S e ru m G ro w th H o rm o n e (n g /m l) Baseline Month 6 Baseline 6 months LUM-201 1.6 mg/kg/d IGF-1 (ng/ml) 179.3 289 % change from baseline** 61% Q10m 12h GH AUC0-12 (ng*hr/ml) 798.8 1064.1 % change from baseline** 33% Height velocity (cm/yr) 5.6 7.9 **Percent change from baseline calculated as: (6mo value – baseline value) / (baseline value) IGF-1, GH Pulsatility, Height Velocity Patient A 1.6 mg/kg/day 22 Patient A Baseline & LUM-201 GH Patient A Serum GH at Baseline & at 6 months on LUM-201
0 200 400 600 800 0 1 2 3 4 5 Patient B Time (min) S e ru m G ro w th H o rm o n e (n g /m l) Baseline 6 months LUM-201 3.2 mg/kg/d IGF-1 (ng/ml) 48 Q10m 12h GH AUC0-12 (ng*hr/ml) 252.9 Height velocity (cm/yr) 4.4 IGF-1, GH Pulsatility, Height Velocity: Patient B 3.2 mg/kg/day 23 Patient B Baseline GH Patient Serum GH at Baseline
0 200 400 600 800 0 1 2 3 4 5 Patient B Time (min) S e ru m G ro w th H o rm o n e (n g /m l) Baseline Month 6 Baseline 6 months LUM-201 3.2 mg/kg/d IGF-1 (ng/ml) 48 111 % change from baseline** 131% Q10m 12h GH AUC0-12 (ng*hr/ml) 252.9 481.8 % change from baseline** 91% Height velocity (cm/yr) 4.4 9.4 **Percent change from baseline calculated as: (6mo value – baseline value) / (baseline value) IGF-1, GH Pulsatility, Height Velocity: Patient B 3.2 mg/kg/day Patient B Baseline & LUM-201 GH 24 Patient B Serum GH at Baseline & at 6 months on LUM-201
Interim Analysis Safety Profile 25 Safety Conclusion: • At time of interim analysis, LUM-201 was well tolerated and showed no significant safety signals Safety Profile: • No treatment-related Serious Adverse Events (SAEs) or Severe AEs • No meaningful safety signals observed in either laboratory values, adverse event data, or in electrocardiogram values. Most Common AEs (% of subjects) noted are: • Transient increased appetite (76.5%) • Pain in extremity (17.6%) • Arthralgia (11.8%) • Abdominal pain (5.9%) • Influenza (5.9%)
Questions 1. Does LUM-201 dose-dependently augment endogenous GH pulses in patients with idiopathic Pediatric Growth Hormone Deficiency (iPGHD)? 2. Will increased amplitude of GH pulsatility, driving increased IGF-1, improve height velocity? 3. Is the effect on AHV durable out to 12 months? 26
Sources: 1 Blum et al JES 2021, 2 Ranke et al JCEM 2010 . 27 • Based on Interim Analysis data, OraGrowtH212 data demonstrates that growth acceleration is durable through 12 months in our study population, pre-pubertal, treatment naïve PGHD patients. • No statistical difference exists between the cohorts at any time point. • Due to some baseline imbalance, the optimal dose cannot be determined from this data set. • We plan to continue the OraGrowtH212 Trial until near adult height. • The observed growth is in line with rhGH historical growth of 8.3-8.6 cm (KIGS 1, GeNeSiS 2) in this moderate idiopathic PGHD population. Conclusions
University of Chile, Santiago Institute of Maternal and Child Research Pediatric Team 28 28
ENDO 2023 – Session OR21-06 Growth Response of Oral LUM-201 in OraGrowtH210 and OraGrowtH212 Trials in Idiopathic Pediatric Growth Hormone Deficiency (iPGHD): Combined Analysis Interim Analysis Data Michael Tansey, MD University of Iowa, Pediatric Endocrinology Iowa City, Iowa 29
Dr. Tansey is an investigator for clinical studies with LUM-201 at the University of Iowa (Sponsor - Lumos Pharma, Inc.). There are no additional disclosures for this presentation. LUM-201 is an investigational compound and is not approved for use by the FDA or any other regulatory agency. Some of the slides in this presentation are derived or copied from corporate presentations previously given by Lumos Pharma, Inc. These slides are used with permission. 30 Disclosure
Abstract Contributors Andrew Dauber, MD, MMSc, Children’s National Hospital, Washington, DC, United States; Beata Wikiera, MD, PhD, Klinika Endokrynologii i Diabetologii Wieku Rozwojowego UM, Wroclaw, N/A, Poland; Beata Pyrzak, MD, Department of Pediatric and Endocrinology Medical University of Warsaw, Warsaw, N/A, Poland; Artur Bossowski, MD, Medical University in Białystok, Białystok, N/A, Poland; Michael Tansey, MD, University of Iowa, Iowa City, IA, United States; Elzbieta Petriczko, MD, Sonomed Clinic, Szczecin, N/A, Poland; Renata Stawerska, MD, Department of Paediatric Endocrinology, Medical University of Lodz, Lodz, N/A, Poland; Sasigarn Bowden, MD, Nationwide Children’s Hospital, Columbus, OH, United States; Alison Lunsford, MD, Texas Tech HSC Amarillo, Amarillo, TX, United States; Matthew Feldt, DO, Children’s Mercy Hospital and Clinics, Kansas City, MO, United States; Michael Everett Gottschalk, MD, PhD, Rady Children's Hospital, San Diego, CA, United States; Monica Marin, MD, Oklahoma Children’s Hospital OU Health, Oklahoma City, OK, United States; Sunil Nayak, MD, Pediatric Endocrine Associates, Greenwood, CO, United States; Bhuvana Sunil, MD, Mary Bridge Children's Hospital and Health Center, Tacoma, WA, United States; Elzbieta Moszczynska, MD, Memorial Institute Children's Health Center, Warsaw, N/A, Poland; David R Repaske, MD, PhD, University of Virginia, Charlottesville, VA, United States; Leslie Soyka, MD, UMass Chan Medical School, Worcester, MA, United States; John Fuqua, MD, Indiana University School of Medicine, Indianapolis, IN, United States; Oscar Escobar, MD, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, United States; Deborah Bowlby, MD, Medical University of South Carolina, Charleston, SC, United States; Patricia Y. Fechner, MD, Seattle Children’s/University of WA, Seattle, WA, United States; Esko Wiltshire, MBChB, MD, FRACP, University of Otago Wellington, Wellington, N/A, New Zealand; Mark Harris, MD, Queensland Children's Hospital, South Brisbane, N/A, Australia Kupper Wintergerst, MD, MBA, University of Louisville, Louisville, KY, United States; Antony R Lafferty, MD, Canberra Hospital and Australian National University Medical School, Canberra, Australia; Bradley S Miller, MD, PhD, University of Minnesota Medical School , Minneapolis, MN, United States; Peter Simm, MD, Royal Children's Hospital, Melbourne, N/A, Australia; Sponsor: Lumos Pharma, Inc., Austin, TX, United States : Aleksandra Bruchey, PhD; Christopher Smith, MS; David B Karpf, MD; John C McKew, PhD; Michael Thorner, BS, DSc, FRCP, MACP, 31
Abstract Contributors Fernando Cassorla, MD, Institute of Maternal and Child Research, University of Chile, Santiago, Chile Rossana Román, MD, Institute of Maternal and Child Research, University of Chile, Santiago, Chile Michael L Johnson, PhD, Emeritus University of Virginia, Charlottesville, Virginia, USA Alejandra Avila, RN, Institute of Maternal and Child Research, University of Chile, Santiago, Chile German Iñiguez, MD, Institute of Maternal and Child Research, University of Chile, Santiago, Chile Ingrid Baier, MD, Institute of Maternal and Child Research, University of Chile, Santiago, Chile Daniela Said, MD, Institute of Maternal and Child Research, University of Chile, Santiago, Chile Sponsor: Lumos Pharma, Inc., Austin, TX, United States : Aleksandra Bruchey, PhD; Christopher Smith, MS; David B Karpf, MD; John C McKew, PhD; Michael Thorner, BS, DSc, FRCP, MACP, 32
Objective of the Presentation Report the growth response analyzing the combined interim analysis (IA) data from two Phase 2 trials studying LUM-201 at two different doses (1.6 mg/kg/day or 3.2 mg/kg/day). IA data from both studies were combined and analyzed for calculated annualized height velocity (AHV). Baseline demographics were analyzed for the two combined cohorts. 33
• Oral LUM-201 is a growth hormone (GH) secretagogue • Acts as a durable agonist of GH Secretagogue Receptor (GHSR1a) to stimulate GH release1 • LUM-201 has been observed to increase the amplitude of endogenous, pulsatile GH secretion over 24 hours2,3 • Another differentiating feature vs rhGH is the natural negative feedback mechanisms, which limit potential for hyperstimulation and excessive increases in IGF-1 • LUM-201 promotes pulsatile GH secretion in a selective PGHD population 1. Howard 1996 Science 273:974-977 2. Nass 2008 Ann Intern Med 149:601-611 3. Chapman 1997 J Clin Endocrinol Metab 82:3455-3463 LUM-201 (ibutamoren) – Mechanism of Action 34
Single Stim Dose of LUM-201 Identifies PEM+ Responders 1 Blum 2021 JES Responders to LUM-201 Non-Responders to LUM-201 Predictive Enrichment Marker Positive (PEM+) • Baseline IGF-1 > 30 ng/ml • Stim LUM-201 peak GH ≥ 5 ng/ml • Functional but reduced HP-GH axis Predictive Enrichment Marker Negative (PEM – ) • Baseline IGF-1 ≤ 30 ng/ml • Stim LUM-201 GH < 5 ng/ml • Non-functional HP-GH axis Moderate / Idiopathic PGHD PEM Positive ~60% of total PGHD population1 Severe / Organic PGHD PEM Negative ~40% of total PGHD population Single Stimulation Dose LUM-201 35
Phase 2 - Dose Finding Study Design Naive Idiopathic PGHD Patients Screening 6, 9, 12, 24 months Height IGF-1 Standard GH stimulation tests Peak GH ≥ 5 ng/ml to single LUM-201 dose Long-term extension study n = ~20 LUM-201-3.2mg/kg/day n = ~20 LUM-201-1.6 mg/kg/day R n = ~20 LUM-201-0.8mg/kg/day n = ~20 daily rhGH injection Study Information • N = 82 subjects • Only PEM (+) pre-pubertal PGHD subjects that are rhGH-treatment naïve • Inclusion: LUM- 201 stim GH > 5 ng/mL & baseline IGF-1 > 30 ng/mL, Previous iPGHD diagnosis, Height < 2 SD, delayed bone age • 45 trial sites US and International • Trial duration: 24 months Feb 28, 2023 enrollment completed Topline 6 mos height velocity data expected 4Q 2023 Primary Endpoints: • Annualized Height Velocity (AHV) Goals: • Prospectively confirm utility of PEM strategy • Determine optimal Phase 3 dose 36
Phase 2 - Pulsatility and PK/PD Study Design Naive Idiopathic PGHD Patients Screening Baseline 6 months Height Height IGF-1 IGF-1 q10m x 12h GH q10m 12h GH Standard GH stimulation test Peak GH to single LUM-201 PEM dose n = 11 LUM-201-3.2mg/kg/day n = 11 LUM-201-1.6 mg/kg/day R Dosing to near Adult Height Study Information • Open-label study: N = 22 • Pre-pubertal PGHD subjects that are rhGH-treatment naïve • Inclusion: Height < 2 SD, delayed bone age, peak GH response to a clonidine stimulation test between 3 and 10 ng • Dosing to near-adult height • Single, specialized clinical site University of Chile, Santiago Primary Endpoints: • Assess LUM-201 effect on endogenous GH pulsatility and Annualized Height Velocity (AHV) • Evaluate PK/PD in children Goals: • Confirm prior PK/PD data in adults & subset of Merck 020 trial • Support future regulatory filings & commercialization 37
Baseline Demographics for OraGrowtH210 and OraGrowtH212 Subjects N=20 1.6 mg N=10 3.2 mg N=10 Mean (SD) Age (mos) 99.3 (28.3) 96.1 (21.7) Height (cm) 114.6 (9.6) 113.8 (8.8) Height SDS -2.35 (0.62) -2.30 (0.48) IGF-1 SDS -1.17 (0.72) -1.39 (0.61) MPH (cm) 166.98 (7.15) 166.20 (8.06) MPH SDS Δ 1.76 (0.60) 1.96 (0.83) BA Delay (yrs) 1.91 (0.53) 2.19 (0.86) BMI (SDS) -0.35 (0.79) -0.70 (0.48) Male/Female% 60/40 40/60 Subjects N=15 1.6 mg N=8 3.2 mg N=7 Mean (SD) Age (mos) 96.9 (11.9) 95.0 (22.7) Height (cm) 115.2 (4.57) 113.1(9.97) Height SDS -2.12 (0.29) -2.34 (0.45) IGF-1 SDS -1.1 (0.535) -0.8 (0.377) MPH (cm) 161.8 (6.98) 160.82 (5.73) MPH SDS Δ 0.73 (0.47) 0.81 (0.43) BA Delay (yrs) 1.50 (0.26) 1.83 (0.88) BMI (SDS) -0.18 (0.96) +0.48 (1.02) Male/Female% 63/37 71/29 These data represent the patient data that had been collected at time of Interim Analysis calculation. No statistically significant differences between cohorts in each trial (unpaired t-test comparing baseline mean/SD) SDS = Standard deviation score MPH = Mid-parental height MPH SDS Δ = MPH SDS-Ht SDS BA = Bone age BMI = Body mass index 38
Annualized Height Velocity of 2 Doses Show Durable Response from 6-12 Months Interim Analysis (IA) Results • Interim data demonstrate LUM- 201 produces durable AHV response from 6 to 12 months in moderate PGHD • LUM-201 at both 1.6 mg/kg and 3.2 mg/kg produces a clinically meaningful increase in AHV from baseline baseline month 6 month 9 month 12 0 4 8 12 14 5.2 17 7.9 11 7.2 7 7.4 17 5.1 18 7.9 11 7.8 8 7.6 m e a n c a lc u la te d A H V ( c m /y r) 1.6 mg/kg 3.2 mg/kg *Pre-treatment baseline AHV was not required for this study but available data shown IA Combined AHV Data from OraGrowtH210 and OraGrowtH212 Trials * 39
1.6 mg/kg 3.2 mg/kg N =33 N=33 Number of AEs 105 110 Subjects with AE (%) 29 (87.9%) 30 (90.9%) Treatment Related AEs * 17 19 Subjects with Treatment Related AEs (%) 12 (36.4%) 13 (39.4%) Subjects with SAEs (%) 0 (0%) 0 (0%) IA Safety Data from Combined Trials Interim Analysis (IA) Results • No treatment-related Serious Adverse Events (SAEs) • No drop-outs due to SAEs or AEs • No meaningful safety signals observed in laboratory values, adverse events data, or in EKG values • Treatment related AEs in both groups: Increased appetite (21), Arthralgia (6), Pain in extremity (6), Abdominal pain (2), Bone pain (1) 40 *
• As the growth velocity was comparable for the two doses of oral LUM-201, this analysis of the combined IA data suggests 1.6 mg/kg/day as the optimal dose for the Phase 3 trial, as doubling the dose appeared to offer no meaningful improvement in efficacy. • Final dose determination will await final full data set analysis of both studies • No treatment-related Serious Adverse Events, no discontinuation due to AEs, and no meaningful safety signals observed in either laboratory values, adverse event data, or in electrocardiogram values. Conclusion 41
42 Questions & Answers