UNITED STATES
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FORM 8-K
CURRENT REPORT
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Item 8.01 Other Events.
On December 12, 2022, Lumos Pharma, Inc. issued a press release titled "KOL Review of Lumos Pharma’s Interim Phase 2 Data Supports Potential for New Oral Therapeutic Paradigm for Moderate Idiopathic PGHD Patients."
A copy of the press release and the slide deck used during the KOL event 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 December 12, 2022, entitled "KOL Review of Lumos Pharma’s Interim Phase 2 Data Supports Potential for New Oral Therapeutic Paradigm for Moderate Idiopathic PGHD Patients." | |||||||
| 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: December 12, 2022
| LUMOS PHARMA, INC., a Delaware corporation | |||||
| By: | /s/ Richard J. Hawkins | ||||
| Richard J. Hawkins | |||||
| Its: | Chief Executive Officer | ||||
KOL Review of Lumos Pharma’s Interim Phase 2 Data Supports Potential for New Oral Therapeutic Paradigm for Moderate Idiopathic PGHD Patients
AUSTIN, TX, December 12, 2022 – Lumos Pharma, Inc. (NASDAQ:LUMO), a clinical-stage biopharmaceutical company focused on rare disorders, hosted two key opinion leaders (KOLs) in the field of pediatric endocrinology on December 6th to review the Company’s interim data from two Phase 2 trials evaluating oral LUM-201 in moderate idiopathic Pediatric Growth Hormone Deficiency (iPGHD). Andrew Dauber, MD, MMSc, Chief of Endocrinology, Children’s National Hospital, and Fernando Cassorla, MD, Chief of Pediatric Endocrinology, University of Chile, discussed recently released (on November 14, 2022) and new interim data (presented on December 6, 2022) from two ongoing OraGrowtH trials.
“Lumos Pharma was delighted to host Drs. Andrew Dauber and Fernando Cassorla, investigators in our OraGrowtH210 and OraGrowtH212 trials, respectively, to share their insights about oral LUM-201 and its potential to treat children with moderate idiopathic PGHD,” said Rick Hawkins, Chairman and CEO of Lumos Pharma. “For the last 40 years, these children have had only injectable growth hormone as a treatment option. In their discussion, both Dr. Dauber and Dr. Cassorla highlighted interim clinical data that supports the potential for LUM-201 as a welcome oral alternative to current therapies that require frequent injections.”
| Replay Links: | KOL Webcast | ||||
Lumos Events & Presentations | |||||
Highlights from Dr. Andrew Dauber’s Discussion of Interim Phase 2 OraGrowtH210 Results
•LUM-201, an oral growth hormone secretagogue, has a unique mechanism of action, targeting specific receptors on the pituitary and hypothalamus to stimulate the natural pulsatile secretion of growth hormone for moderate idiopathic PGHD patients with an intact pituitary-hypothalamic axis
•Reviewed the Interim Phase 2 OraGrowtH210 data announced on November 14, 2022. Reiterated that the annualized growth of 8.6 cm/year at 6 months on 1.6 mg/kg/day of LUM-201 met expectations of 8.3-8.5 cm/year annualized growth at 12 months on therapy established across multiple large datasets of moderate idiopathic PGHD patients on daily rhGH1,2,3,4
•Outsized growth in the trial’s control arm of 10 subjects was likely due to imbalances of baseline characteristics in that arm compared to the 31 subjects across the LUM-201 arms and would likely resolve at full enrollment of 80 subjects in the Phase 2 trial and would not likely be repeated in a large Phase 3 trial
•Safety and tolerability for LUM-201 appear comparable to rhGH in this study period
Highlights from Dr. Fernando Cassorla’s Discussion of Interim PK/PD OraGrowtH212 Results
•New data: A stimulation dose of 0.8 mg/kg LUM-201 produces a substantial growth hormone (GH) response
•New data: LUM-201 at 1.6 and 3.2 mg/kg/day produced a substantial increase in height velocity at 6 months versus baseline for all 10 subjects evaluated in the interim analysis of the OraGrowtH212 Trial
•New data: Substantial increases in growth hormone (GH) area under the curve (AUC) and IGF-1 levels at 6 months on both doses of LUM-201 compared to baseline were also observed
•New baseline data showing age and Height SDS values for OraGrowtH212 was presented which suggest that the 3.2 mg cohort was somewhat more growth hormone deficient than the 1.6 mg cohort, likely explaining the seemingly faster growth seen in the 3.2 mg/kg/day LUM-201 cohort
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.
Drawing from their experience in the clinic, Dr. Dauber and Dr. Cassorla noted the compliance issues with the injectable growth hormone, the only current treatment option for PGHD, supporting the potential for an oral therapeutic like LUM-201 to potentially improve compliance for their moderate idiopathic PGHD patients. Both doctors commented that there were also a number of patients currently not receiving treatment for PGHD because of their aversion to injections. Dr. Dauber and Dr. Cassorla acknowledged that it was likely that an oral therapeutic like LUM-201 would appeal to this latter population, potentially expanding the market for PGHD therapies.
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 and received early funding from leading healthcare investors, including Deerfield Management, a fund managed by Blackstone Life Sciences, Roche Venture Fund, New Enterprise Associates (NEA), Santé Ventures, and UCB. Lumos Pharma’s lead therapeutic candidate is LUM-201, an oral growth hormone stimulating small molecule, currently being evaluated in a Phase 2 clinical trial, the OraGrowtH210 Trial; a PK/PD trial, the OraGrowtH212 Trial; and a switch trial, the OraGrowtH213 Trial for the treatment of Pediatric Growth Hormone Deficiency (PGHD). If approved by the FDA, LUM-201 would provide an orally administered alternative to recombinant growth hormone injections that PGHD patients 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/.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements of Lumos Pharma, Inc. that involve substantial risks and uncertainties. All such statements contained in this press release are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. A law that, in part, gives us the opportunity to share our outlook for the future without fear of litigation if it turns out our predictions were not correct.
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 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, expecting the primary outcome data readout for our trials, the potential to expand our LUM-201 platform into other indications, anticipated market reception to our treatment regimen for PGHD and other indications, plans related to initiation and execution of clinical trials; plans related to moving additional indications into clinical development; future financial performance, results of operations, cash position and sufficiency of capital 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. Forward-looking statements contained in this announcement are made as of this date and Lumos undertakes no duty to update such information except as required under applicable law. 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 Lumos Pharma’s Annual Report on Form 10-K for the year ended December 31, 2021, as well as other reports filed with the SEC including our Quarterly Reports on Form 10-Q. 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 press release.
###
Investor & Media Contact:
Lisa Miller
Lumos Pharma Investor Relations
512-792-5454
ir@lumos-pharma.com
1 KOL Event December 6, 2022
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 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 trails 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, 2021, 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. 11.12.2022
3 Investment Highlights Lead asset targeting children with growth disorders PGHD = Pediatric Growth Hormone Deficiency * USA, Germany, France, Italy, Spain, UK, Japan (Grandview Research, Growth Hormone Market Forecast, 2019) 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 • Potential to disrupt significant subset of sizable injectable market for GHD • Worldwide injectable market for GHD disorders is $3.4 billion* • Market for initial oral LUM-201 indication, Pediatric GHD (PGHD), is $1.2 billion* • Prior data support potential efficacy of LUM-201 in multiple GHD disorders • Cash balance of $73.7 million as of close of 3Q 2022 • Cash runway into 2Q 2024, beyond OraGrowtH210 & OraGrowtH212 primary outcome data Late-stage Trials in PGHD • Phase 2 OraGrowtH210 Trial & PK/PD OraGrowtH212 Trials ongoing • Interim data obtained | Primary outcome data expected 2H 2023 • Approximately 80% enrolled in Phase 2 OraGrowtH210 Trial
4 Key Opinion Leaders in the Field of Pediatric Endocrinology Andrew Dauber, M.D., M.M.Sc., is the Chief of Endocrinology at Children’s National Hospital, specializing in growth disorders. Dr. Dauber has served as the program director and director of translational research at the interdisciplinary Cincinnati Center for Growth Disorders at Cincinnati Children’s Hospital Medical Center. Additionally, he was the director of their Genomics First for Undiagnosed Diseases Program and guided medical residents and fellows as an associate professor of pediatrics at the University of Cincinnati. He held similar roles as the assistant medical director for the clinical research unit at Boston Children’s Hospital and as an assistant professor in pediatrics at Harvard Medical School. Dr. Dauber has authored over 100 publications and is an active member of the Endocrine Society, Pediatric Endocrine Society, European Society of Pediatric Endocrinology and the Society for Pediatric Research, having received several awards and honors from these entities. Dr. Dauber received his M.D. and Master’s of Medical Sciences in Clinical Investigation from Harvard Medical School. 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, he 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. Dr. Cassorla 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, including the ESPE International Research Award, September 2022, and was elected to the Chilean Academy of Medicine for a lifetime position in 2003.
Andrew Dauber, M.D., M.M.Sc. OraGrowtH210 Trial
Review of Interim Data for Phase 2 OraGrowtH210 Trial Andrew Dauber, MD MMSc Chief of Endocrinology Children’s National Hospital Evaluation of Oral LUM-201 in Moderate Idiopathic Pediatric Growth Hormone Deficiency (PGHD) 6
Disclosures • Consulting fees or speaker honoraria: – Ascendis, OPKO, BridgeBio, Novo Nordisk, Pfizer, Ipsen, Sandoz • Prior Research Support – Novo Nordisk, Ipsen, Pfizer • Current Research Support – BioMarin, NICHD, Pfizer • Site Investigator in Lumos OraGrowth210 Trial 7
LUM-201 –Oral Growth Hormone Secretagogue https://lumos-pharma.com/posters-publications/ ClinicalTrials.gov NCT04614337. LUM-201 • Binds to GH Secretagogue (ghrelin) receptor • Increases amplitude of endogenous GH pulses • Acts within intact GH/IGF-1 feedback loop • Phase 2 study ongoing • 3 doses of LUM-201 vs daily rhGH • 24-month study • Pre-pubertal GH deficiency LUM-201 8
Single Stim Dose of LUM-201 Identifies Likely Responders Responders to LUM-2012 Non-Responders to LUM-201 Moderate / Idiopathic PGHD PEM-Positive ~60% of total PGHD population1 Severe / Organic PGHD PEM-Negative ~40% of total PGHD population 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 Stim dose 1 Blum 2021 JES 2 Bright 2021 JES HP-GH axis – hypothalamic pituitary growth hormone axis LUM-201 LUM-201 LUM-201 9
Phase 2 OraGrowtH210 Trial in Moderate Idiopathic PGHD n = 20 Daily rhGH injection n = 20 LUM-201: 3.2 mg/kg/day n = 20 LUM-201: 1.6 mg/kg/day n = 20 LUM-201: 0.8 mg/kg/day R a n d o m i z a t i o n Trial Design ❖ N = 80 subjects ❖ Only PEM(+) PGHD subjects ❖ Inclusion: stim GH > 5 ng/mL* & baseline IGF-1 > 30 ng/ML ❖ rhGH treatment naïve ❖ ~45 trial sites US & Int’l ❖ Trial opened Q4 2020 ❖ Trial duration 24 months * Peak GH response to single stimulation dose of 0.8 mg/kg dose of LUM-201 Trial Objectives Primary Endpoint ❖ Annualized Height Velocity (AHV) Goals ❖ Prospectively confirm utility of PEM strategy ❖ Determine optimal Phase 3 dose Interim Data: 41 subjects @ 6 months on therapy – November 2022 Primary Outcome Data: 80 subjects @ 6 months on therapy – 2H 2023 10
Historical Data for rhGH Growth Rates 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) Historical Datasets • GeNeSIS1, iPGHD2, and KIGS3 AHV at 12 months on rhGH • Merck 0204 AHV at 6 months on rhGH • These historical trials set precedent for expected growth on rhGH in moderate idiopathic PGHD Predictions • Prediction for growth in OraGrowtH210 is AHV of ~8.3 cm/yr on both rhGH and LUM-201 based on this historical data Merck Eli Lilly PfizerSpain study 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. 11
OraGrowtH210 Interim Analysis: AHV at 6 Months (41 Subjects) Interim Results • 1.6 mg/kg/day LUM-201 cohort growth of 8.6 cm/year was in line with the expected rate of 8.3-8.5 cm/year based on historical data • rhGH cohort grew at a much faster rate than expected or previously reported in moderate idiopathic PGHD population • Cohort baseline differences predict faster first- year growth in the rhGH arm1,2 • Median AHV values offer more authentic comparison by minimizing impact of outliers • Further enrollment of trial likely to even out baseline imbalances and produce more similar growth across cohorts 1 Blum et al JES 2021, 2 Ranke et al JCEM 2010 7.26 (7.71) 8.57 (8.61) 7.77 (8.11) 11.05 (10.48) Mean (Median) AHVs 12
OraGrowtH210 Baseline Characteristics at Interim (n=41) LUM-201 0.8 mg Mean (SD) N=11 LUM-201 1.6 mg Mean (SD) N=10 LUM-201 3.2 mg Mean (SD) N=10 rhGH Mean (SD) N=10 Age (months) 95.5 (28.2) 99.3 (28.3) 96.1 (21.7) 90.3 (26.7) Height (cm) 113.8 (12.6) 114.6 (9.6) 113.8 (8.8) 111.6 (11.9) Height SDS -2.31 (0.32) -2.35 (0.62) -2.30 (0.48) -2.29 (0.43) Max Height SDS -1.76 -1.66 -1.57 -1.73 IGF-1 SDS -1.24 (0.573) -1.17 (0.72) -1.39 (0.61) -1.37 (0.48) Max IGF-1 SDS -0.3 -0.3 -0.6 -0.7 MPH (cm) 164.47 (6.44) 166.98 (7.15) 166.20 (8.06) 168.78 (8.85) MPH SDS ∆ 1.29 (0.62) 1.76 (0.60) 1.96 (0.83) 1.76 (0.73) BA Delay (yrs) 1.89 (1.02) 1.91 (0.53) 2.19 (0.86) 1.78 (0.96) BMI SDS1 -0.29 (1.04) -0.35 (0.79) -0.70 (0.48) +0.31 (1.05) 1 Yang, et al. Nature Sci Rep 2019, 9(1); 16181 2 Ranke et al JCEM 2010 SDS = Standard deviation score | MPH = Mid-parental height (Child’s target height) | MPH SDS delta = SD’s from target height | BA = Bone age | BMI = Body mass index • Imbalances were observed in baseline characteristics between rhGH arm & LUM-201 arms • Baseline characteristics predict faster 1st year growth on therapy for rhGH arm than for LUM-201 arms2 13
Growth Outliers in the rhGH Cohort: Two of Three Subjects Under Age 5 Randomized to rhGH 1 Ranke, et al 2010 JCEM P lines = Percentiles “Before” line marks height velocity before GH therapy First-year Growth on rhGH for Pfizer’s Moderate PGHD KIGS Database Analysis1 OraGrowtH210 youngest subjects in rhGH cohort at 6-months AHV 14
Interim OraGrowtH210 Data: LUM-201 Demonstrates Durable Response to 12 Months 0.8 1.6 3.2 rhGH 0 4 8 12 16 20 7 10.46 6 6.80 6 8.48 5 6.17 A n n u a li z e d H e ig h t V e lo c it y ( c m /y r) 9-month AHV mg/kg LUM-201 Conclusions • Growth rates for LUM-201 are consistent from 6 to 12 months • A Phase 3 non-inferiority trial is expected to be a 12-month study in a significantly larger population • Historically, non-inferiority margin for AHV’s in Phase 3 trials was ~2 cm 15
Safety Profile at Interim Analysis for OraGrowtH210 Trial 0.8 mg/kg 1.6 mg/kg 3.2 mg/kg ALL LUM-201 rhGH 34 mcg/kg N = 14 15 14 43 15 Number of AEs 31 45 38 114 21 Subjects with AE (%) 8 (57.1%) 13 (86.7%) 9 (64.3%) 30 (69.8%) 9 (60.0%) Treatment Related AEs (N) 2 1 3 6 3 Subjects with Treatment Related AEs (%) 1 (7.1%) 1 (6.7%) 2 (14.3%) 4 (9.3%) 2 (13.3%) Subjects with SAEs (%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Data Available • Data available for 58 subjects at time of interim analysis • 66 subjects total enrolled at time of interim analysis 16
Summary of Interim OraGrowtH210 Data • Growth of 8.6 cm/yr on 1.6 mg LUM-201 in line with expectations • 9 and 12-month growth data look encouraging for LUM-201, but N is small • Interim safety data appear comparable to rhGH treatment 17
Fernando Cassorla, M.D. OraGrowtH212 Trial
Fernando Cassorla MD Chief of Pediatric Endocrinology Institute of Maternal and Child Research University of Chile, Santiago, Chile Effects of the oral growth hormone (GH) secretagogue LUM-201 (Ibutamoren) on pulsatile GH secretion and linear growth in children with moderate GH deficiency 19
Disclosure Fernando Cassorla M.D. Dr. Cassorla is an investigator for clinical studies with LUM-201 at the University of Chile and has previously acted as a consultant for Debiopharm, Novo Nordisk, Pfizer, Merck 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. 20
▪ Does the oral administration of LUM-201 at the doses of 1.6 mg/kg or 3.2 mg/kg for 6 months increase height velocity? ▪ Is the change in height velocity correlated with changes in GH pulsatility? ▪ Is the increase in GH pulsatility and height velocity induced by LUM-201 dose dependent? Questions regarding the effects of LUM-201 in pediatric patients with moderate growth hormone deficiency: 21
• 24 prepubertal patients between the ages of 4 to 8 years (girls) and 10 years (boys) with short stature caused by moderate idiopathic PGHD, and naïve to GH treatment, will be randomized to receive oral LUM-201 at a dose of 1.6 mg/kg/day (n:12) or 3.2 mg/kg/day (n:12) • Pulsatile GH secretion has been assessed in blood samples obtained every 10 minutes over 12 hours (8 AM to 8 PM), at the beginning and after 6 months of LUM-201 therapy • Height velocity during the 6 months of LUM-201 administration has been compared with a baseline period prior to intervention Design of the OraGrowtH212 clinical PK/PD study of LUM-201 in naïve pediatric patients with moderate GH deficiency 22
LUM-201 1.6 mg/kg/day N=12 Screening Baseline 6 months Height Height IGF-1 IGF-1 Q10m 12h GH Q10m 12h GH Inclusion Criteria: Height < 2 SD, delayed bone age, serum IGF-1 below the mean for age, and a peak GH response to a clonidine stimulation test between 3 and 10 ng/mL ** Peak GH response to a single LUM-201 0.8 mg/kg dose was also assessed in screening. Standard GH stimulation tests Peak GH to single LUM-201 dose LUM-201 in naïve prepubertal patients with GH deficiency Standard GH stimulation tests Peak GH to single LUM-201 dose** LUM-201 3.2 mg/kg/day N=12 Screening Baseline 6 months Height Height IGF-1 IGF-1 Q10m 12h GH Q10m 12h GH 23 OraGrowtH212 Trial
OraGrowtH212 Patient Baseline Characteristics • Mean Height SDS is lower in the 3.2 mg cohort than in the 1.6 mg cohort • 3.2 mg cohort subjects appear to be more growth hormone deficient than subjects in the 1.6 mg cohort • Differences between cohorts suggest faster growth on treatment for 3.2 mg subjects 24 Patient Gender Age (months) Dose (mg/kg) Height (SDS) Clonidine test (GH ng/mL) PEM test (GH ng/mL) time 0 peak peak 801-101 F 91 3.2 -2.39 8.2 32 801-102 M 74 3.2 -3.12 5.8 22.7 801-103 M 105 3.2 -1.85 3.1 18.2 801-104 F 97 1.6 -1.76 5.1 24.3 801-105 M 97 1.6 -1.85 7.8 23.7 801-106 F 63 3.2 -1.95 9.6 36.1 801-107 M 80 1.6 -2.14 9.8 21.5 801-108 F 89 1.6 -2.32 6.5 21.5 801-109 M 122 3.2 -2 7.5 19.5 801-110 M 105 1.6 -1.88 9.9 40.3
Height velocity before and after 6 months of LUM-201 administration pre-treat LUM-201 6 mo 0 4 8 12 A n n u a li z e d H e ig h t V e lo c it y ( c m /y r) 25 AHV Change in OraGrowtH212 Trial
Height velocity after 6 months of LUM-201administration A n n u a li z e d H e ig h t V e lo c it y ( c m /y e a r) 7.14 cm 8.60 cm 26 Mean AHV’s in OraGrowtH212 Trial
Durable response after 12 months of LUM-201 administration • OraGrowtH212 data demonstrate that growth acceleration is durable up to 12 months • This separate study supports the narrowing of the AHV difference seen in the 210 trial as subjects approach 12 months on treatment • A Phase 3 non-inferiority trial is expected to be a 12-month study in a much larger population 27 Mean AHV’s in OraGrowtH212 Trial
▪ Does the oral administration of LUM-201 at the doses of 1.6 mg/kg or 3.2 mg/kg over 6 months increase height velocity? √ ▪ Is the change in height velocity correlated with changes in GH pulsatility? ▪ Is the increase in GH pulsatility and height velocity induced by LUM-201 dose dependent? Questions regarding the effects of LUM-201 in pediatric patients with moderate growth hormone deficiency: 28
Prior PK/PD Data Show LUM-201 Pulsatile MOA & Potential Efficacy in Moderate Idiopathic PGHD * Merck Study 020 patient subset. Cassorla, F. 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 0 6 12 18 24 30 Sampling Time (hr) S e ru m G ro w th H o rm o n e ( n g /m l) Patient A Baseline 6 months PEM-Positive Patient A • Prior PK/PD data in PEM+ subjects demonstrate pulsatile MOA of LUM-201 • Data show at 6 months, LUM-201 amplifies baseline GH peaks and increases serum GH AUC • In prior PK/PD study, blood samples were taken every 20 minutes over 24- hour period inclusive of significant GH secretion known to occur at night • GH secretion is not symmetric between day and nighttime hours and is not scalable to 24-hour secretion from our data PEM+ PGHD patient administered 0.8 mg/kg/day LUM-201 for 6 months* NightDay Q20m 24h GH 29
Percent change from baseline in GH area under the curve (AUC) after 6-months of LUM-201 administration at doses of 1.6 or 3.2 mg/kg/day 30 LUM-201 Dose 1.6 mg/kg/day 3.2 mg/kg/day Subjects (N) 4 5 Mean Change in GH AUC from Baseline 34% 197% GH Interim Data from OraGrowtH212 Trial
Patient 105 – 1.6 mg/kg 31 Q10m 12h GH 0 200 400 600 800 0 2 4 6 8 Patient 105 Time (min) S e ru m G ro w th H o rm o n e (n g /m l) Baseline Baseline 6 months LUM-201 1.6 mg/kg/d IGF-1 (ng/ml) 110 Q10m 12h GH AUC0-12 (ng*hr/ml) 273 Height velocity (cm/yr) 4.6 Interim Data from OraGrowtH212 Trial
Baseline 6 months LUM-201 1.6 mg/kg/d IGF-1 (ng/ml) 110 185 Q10m 12h GH AUC0-12 (ng*hr/ml) 273 724 Height velocity (cm/yr) 4.6 6.8 Patient 105 – 1.6 mg/kg 32 Q10m 12h GH 0 200 400 600 800 0 2 4 6 8 Patient 105 Time (min) S e ru m G ro w th H o rm o n e (n g /m l) Baseline Month 6 Interim Data from OraGrowtH212 Trial
Patient 103 – 3.2 mg/kg 33 Q10m 12h GH 0 200 400 600 800 0 5 10 15 Patient 103 Time (min) S e ru m G ro w th H o rm o n e (n g /m l) Baseline Baseline 6 months LUM-201 3.2 mg/kg/d IGF-1 (ng/ml) 124 Q10m 12h GH AUC0-12 (ng*hr/ml) 276 Height velocity (cm/yr) 3.4 Interim Data from OraGrowtH212 Trial
Patient 103 – 3.2 mg/kg 34 Q10m 12h GH 0 200 400 600 800 0 5 10 15 Patient 103 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) 124 262 Q10m 12h GH AUC0-12 (ng*hr/ml) 276 1959 Height velocity (cm/yr) 3.4 8.3 Interim Data from OraGrowtH212 Trial
IGF-1 serum concentrations after daily LUM-201 administration in OraGrowtH212 Trial 35 baseline month 1 month 3 month 6 month 12 0 100 200 300 400 8 121 7 214 5 254 5 226 4 215 9 114 8 191 7 199 4 196 2 244 M e a n I G F -1 c o n c e n tr a ti o n ( n g /m L ) 1.6 mg/kg 3.2 mg/kg
- We have documented an increase in the height velocity compared to baseline in a group of prepubertal patients with moderate GH deficiency treated with two doses of LUM-201 - The improved height velocity during LUM-201 administration appears to be correlated with an increase in GH pulsatility after 6 months of therapy with this drug - In this limited sample size, these preliminary findings suggest that the changes in height velocity and GH pulsatility induced by LUM-201 may be dose-dependent 36 OraGrowtH212 Interim results
Institute of Maternal and Child Research Pediatric Team, University of Chile 37
Rick Hawkins, CEO & Chairman Lumos Pharma, Inc.
39 OraGrowtH212 & OraGrowtH210 Comparative AHVs at 6 Months • OraGrowtH212 Trial results showed a similar growth rate to that seen in the OraGrowtH210 Trial • Anticipate fully enrolled datasets and larger N from both trials to strengthen these results • Anticipate larger Phase 3 trial to further support the LUM-201 AHVs seen in both OraGrowtH210 & OraGrowtH212 trials Conclusions OraGrowtH210OraGrowtH212
40 OraGrowtH210 & OraGrowtH212 Interim Data Combined • Post-hoc analysis of combined data conducted to determine optimal dose for Phase 3 • Comparable mean AHVs for top 2 LUM-201 doses seen at 6, 9, and 12 months • Combined interim data supports selection of 1.6 mg/kg/day dose for pivotal Phase 3 trial Conclusions Annualized Height Velocity for LUM-201 Combined Data from OraGrowtH210 & OraGrowtH212 Trials 1.6 3.2 0 4 8 12 16 20 15 8.05 15 8.09 A n n u a li z e d H e ig h t V e lo c it y ( c m /y r) mg/kg LUM-201 6 month AHV 1.6 3.2 0 4 8 12 16 20 10 7.28 10 7.83 A n n u a li z e d H e ig h t V e lo c it y ( c m /y r) 9 month AHV mg/kg LUM-201 1.6 3.2 0 4 8 12 16 20 6 7.36 6 7.83 A n n u a li z e d H e ig h t V e lo c it y ( c m /y r) 12 month AHV mg/kg LUM-201
41 Interim Analysis: LUM-201 Met Expectations in Idiopathic (PEM+) PGHD SAEs = Serious adverse events AEs = Adverse events • AHV of 8.6 cm at 6-months on 1.6 mg/kg/day LUM-201, in line with 8.3 cm expected in PEM+ PGHD • LUM-201 AHVs are sustained & converge with rhGH AHVs at 12-month treatment interval • No treatment related SAEs, no trial dropouts due to AEs, and no meaningful safety signal • Interim safety and efficacy data support selection of 1.6 mg/kg/day for Phase 3 • ~$3.4 billion worldwide GHD market treated by injectable rhGH primed for conversion to oral therapy Expected annualized height velocity (AHV) was met Durability of growth response was observed at 9 and 12 months Safety and tolerability profile Evidence of a dose response & Phase 3 dose identified Data support potential for oral LUM-201 to disrupt injectable PGHD market
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