Therapeutics For Rare Diseases - Lumos Pharma

1

Therapeutics For Rare Diseases

March 2022

2

Forward Looking Statements

This presentation contains forward-looking statements of Lumos Pharma, Inc. that involve substantial risks and uncertainties. All such statements contained inthis presentation are forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, a law that gives us the opportunity toshare 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 ourefforts 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 statementscontain these identifying words. Examples of forward-looking statements include, among others, statements we make regarding screening and enrollment forboth our OraGrowtH210 and OraGrowtH212 Trials progressing well, anticipating interim analyses of OraGrowtH210 and OraGrowtH212 Trials by the end of2022, 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 ourOraGrowtH210 Trial in the second half of 2023, the potential to expand our LUM-201 platform into other indications, future financial performance, results ofoperations, cash usage and cash position and sufficiency of our cash resources to fund our operating requirements through the primary outcome data readoutfrom 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. In addition to other considerations referenced in this paragraph, therecent conflict between Ukraine and Russia has increased the uncertainty in that region and may impact our business in the future. Our forward-lookingstatements are neither historical facts nor assurances of future performance. Actual results or events could differ materially from the plans, intentions andexpectations disclosed in the forward-looking statements that we make due to a number of important factors, including the effects of pandemics, otherwidespread health problems or the Ukraine-Russia conflict, the outcome of our future interactions with regulatory authorities, our ability to project future cashutilization and reserves needed for contingent future liabilities and business operations, the ability to obtain the necessary patient enrollment for our productcandidate in a timely manner, the ability to successfully develop our product candidate, the timing and ability of Lumos to raise additional equity capital asneeded and other risks that could cause actual results to differ materially from those matters expressed in or implied by such forward-looking statements. Youshould not rely on any of these forward-looking statements and, to help you make your own risk determinations, we have provided an extensive discussion ofrisks that could cause actual results to differ materially from our forward-looking statements in the "Risk Factors" section and elsewhere in Lumos Pharma’sAnnual Report on Form 10-K for the year ended December 31, 2020, 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 somepoint 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 viewsas of any date subsequent to the date of this presentation. 3.10.2022

3

Investment Highlights

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

• Prior data support potential efficacy and safety of LUM-201 across multiple indications

• Potential to disrupt significant subset of sizable injectable market for GHD

• Worldwide market for GHD disorders is $3.4 billion*

• Market for initial oral LUM-201 indication, PGHD, is $1.2 billion*

• Cash balance of $94.8 million at close of Q4 2021

• Cash runway through primary outcome data for OraGrowtH210 & OraGrowtH212 Trials

Late-stage

Trials in PGHD

• OraGrowtH210 Trial (Phase 2):

• OraGrowtH212 Trial (PK/PD):

• OraGrowtH213 Trial (Switch):

Interim data by year-end 2022 | Primary data 2H2023

Interim data by year-end 2022

Initiated

4

Bob Davis, PharmD VP, Clinical Operations

Responsible for developing global development

strategy and execution at Sensus for GH Receptor

antagonist for acromegaly (approved in US,

Europe, Japan), diabetes, and diabetes retinopathy.

Previously Executive Director at Pharmaco; Senior

Director at Searle: Senior Scientist at Parke-Davis.

Lori Lawley, CPA CFO

Former SVP, Finance and Controller at Lumos

Pharma. Previously, SVP, Finance and Member of

the Office of the CEO of NewLink Genetics. Prior to

that, Senior Manager in Assurance Services at

Ernst and Young.

John McKew, PhD President & CSO

Prior VP of Research at aTyr Pharma – led team

advancing protein-based therapeutics for rare

diseases. Former Scientific Director, NIH - National

Center for Advancing Translational Science

(NCATS) and Therapeutics for Rare and Neglected

Diseases (TRND). Director level, Wyeth Research

Genetics Institute.

Aaron Schuchart, MBA CBO

Former CBO of Aeglea BioTherapeutics, former

leadership roles in Business Development,

Strategy, and Finance at Coherus Biosciences,

Novartis Diagnostics/Grifols, and Amgen.

David Karpf, MD Chief Medical Officer

Adjunct Clinical Professor, Endocrinology, Stanford

University School of Medicine. Former VP, Clinical

Development at Ascendis Pharma; projects include

long-acting TransCon GH and PTH injectables,

among other compounds. Prior biotech CMO.

Clinical R&D leadership roles at Roche and Merck.

Conducted clinical research on LUM-201 at Merck.

Management – Significant Clinical Development and Commercial Experience

Richard Hawkins Chairman & CEO

Developed Growth Hormone (GH) Receptor

Antagonist for Acromegaly at Sensus (sold to

Pfizer). Built one of the first contract recombinant

protein manufacturing facilities (Covance

Biotechnology). Co-founded Pharmaco, a contract

research organization (merged with PPD).

5

LUM-201 Program Pipeline

Study Pre-Clinical Phase 1 Phase 2 Phase 3 Status

LUM-201(Ibutamoren)

In PGHD

Phase 2Ongoing Phase 2 trial: Interim analysis anticipated

by year-end 2022 | Primary outcome data 2H2023

Long-term

extension

Proposed long-term extension study for

OraGrowtH Trials

PK/PD trial PK/PD trial: Interim analysis anticipated by

year-end 2022

Switch trialSwitch trial evaluating LUM-201 in subjects from

rhGH arm of OraGrowtH210 Trial: Initiated

Lumos is evaluating additional indications for LUM-201 for Phase 2 studies

Small for Gestational Age Prader-Willi Syndrome Turner Syndrome Idiopathic Short Stature

PGHD Pediatric Growth Hormone Deficiency

6

PGHD is ~35% of the $3.4B Pediatric Recombinant Growth Hormone Market

• Pediatric rhGH market projected to grow ~8% per year*

• Well characterized market with established reimbursement mechanisms

• Current SOC consists of daily injectables; expected to convert to weekly injectables

• Pediatric rhGH market appears primed for conversion to oral therapy

*Grandview Research, hGH Market, 2018, excludes Adult Growth Hormone Deficiency

PGHD

$1,164

Turner

Syndrome

$817

SGA $232

Other $133

Prader-

Willi $279

Idiopathic

Short

Stature

$791

US $566

EU $311

APAC $208

ROW

$92

2018 Global rhGH Sales $3.4B*(Values below in $millions)

2018 Sales of rhGH for PGHD $1.2B*(Values below in $millions)

7

Pediatric Growth Hormone Deficiency (PGHD) – Conversion from Injection to Oral

1 GlobalData EpiCast Report for Growth Hormone Deficiency Epidemiology forecast to 20262 Rosenfeld 2008 Endocrine Practice3 Cutfield 2011 PLOS ONE

• Inadequate secretion of growth

hormone during childhood

• Majority of cases are idiopathic

• Slower physical growth

• Negative effect on metabolic

processes

• Incidence ≈ 1:35001

• Injectable therapies are only options

• Daily, subcutaneous injections of

recombinant human growth hormone

(rhGH) represent standard of care

• Weekly rhGH injections are entering

the market

• Standard treatment is ~2,500 daily

injections over multi-year period

• Injections can be painful and burdensome

• Missed doses lead to suboptimal growth2,3

• Initial market research supports oral

therapy vs weekly injections

PGHD Current Treatment Unmet Need

An established market is now primed for the first oral alternative

8

Market Research: Daily Oral Therapeutic Preferred Over Weekly Injectable

1 Initial Primary Research of PGHD Market conducted for Lumos by Triangle Insights. Physicians N = 20. Caregivers N = 9.

75%

25%

Interview Question:

If a daily oral secretagogue and a weekly

rhGH injectable product were both FDA-

approved and available for use, which

product would you prefer?67%

33%Daily Oral

Weekly Injectable

Physicians Caregivers

Consideration Market Research Findings1

Unmet Need Non-injectable (oral) therapy; Less frequent administration of injectable therapy

Preference Vast majority of physicians & caregivers surveyed prefer daily oral tablet over weekly injectable

MOA Favorable impression regarding LUM-201 affecting natural physiology vs bolus rhGH treatment

Treatment Decisions Collaborative between physicians and caregivers

Payer Decisions Price policies in place for category – small molecule COGS should provide attractive margins

9

LUM-201 Stimulates Endogenous GH Secretion vs. Exogenous rhGH Injection

• LUM-201 is an oral growth hormone (GH)

secretagogue

• Agonist of GPCR GH Secretagogue

Receptor 1a (GHSR1a)

• Stimulates release of GH1

• Increases the amplitude of endogenous

pulsatile GH secretion2,3

• Stimulatory effect is regulated by

endogenous GH/IGF-1 feedback

• Differentiated from bolus injection of

recombinant human growth hormone

(rhGH) products

1 Howard 1996 Science 2 Nass 2008 Ann Intern Med 3 Chapman 1997 J Clin Endocrinol Metab

Pituitary

IGF-1

Hypothalamus

GH

SR

1a

GH

SR

1a

Growth

Hormone

SST GHRH

SST somatostatin

GHRH growth hormone-releasing hormone

GPCR G protein-coupled receptor

IGF-1 insulin-like growth factor-1

GHSR1a GH secretagogue receptor 1a

LUM-201

10

PEMs Enrich Trials for Patients with Functional but Reduced GH Secretion

HP-GH – hypothalamic pituitary growth hormone 1 Bright 2021 JES 2 Blum 2021 JES

Moderate (PEM+): Included in Clinical Trials Severe (PEM ): Excluded from Clinical Trials

Predictive Enrichment Markers (PEMs): Data demonstrate GH response to single

LUM-201 dose and baseline IGF-1 have potential to distinguish these populations

IGF-1

Pituitary

Hypothalamus

GH

SR

1a

GH

SR

1a

GH

SST GHRH

Pituitary

Hypothalamus

GH

SR

1a

GH

SR

1a

GH

SST GHRH

Non-functional HP-GH axis

o Unable to secrete GH

o Not expected to respond to LUM-201

o Represents ~40% of PGHD patients2

LUM-201 LUM-201

Functional but reduced HP-GH axis

o Able to secrete some, but insufficient, GH

o Expected to respond to LUM-2011

o Represents ~60% of PGHD patients2

11

Growth Hormone Deficiency Patients Have a Range of Secretion Insufficiency

• Well established in the literature:

o A wide range of severity in GHD1

o Variability in responses to GH therapy

o Severely deficient patients exhibit greater growth response to rhGH compared to moderately deficient patients1

• Several prediction models attempt to explain variability and optimize GH treatment2

o Multiple factors may contribute

o GH response to standard stimulation tests is most important predictor of first year growth response to rhGH in PGHD in one analysis3

o Inclusion of baseline IGF-1 strengthened model4

• Recent publications

o Baseline IGF-1 and GH response to standard stimulations tests are independent predictors of growth when patients are treated with rhGH5

o Moderate GHD represents ~60% of total PGHD population5

1 Tanner 1971 Arch Dis Childhood 2 Wit 2013 Hormone Res Paed3 Ranke 1999 JCEM4 Kristrom 1997 JCEM5 Blum 2021 JES

…as defined by

baseline IGF-1

…and as defined

by GH response to

standard stim tests

Differential rhGH response according to GHD severity

12

PEM Segmentation Aligns With Patients’ Differentiated Baseline Characteristics

PEM Predictive Enrichment Marker SDS Standard Deviation Score 1 Blum 2021 JES; mean growth after 1 year of treatment 2 Bright 2021 JES

Severe

38%

Moderate

62%

GeNeSIS1

12,315 GHD

514 isolated GHD

BaselineChronological age (y) 6.80 7.10

Height SDS -3.01 -2.58

rhGHHeight velocity (cm/y) 9.62 8.29


Analysis of 20-yr multinational

database for Eli Lilly’s rhGH:

Illustrate PGHD population can be

segmented by severity

• Segmentation achieved using

PEMs (markers) IGF-1 and peak

GH to stimulation tests

• Moderate and Severe have

distinct characteristics

Lumos PEMs applied to GeNeSIS

show Moderates ~60% of PGHD

• Likely LUM-201 responders

• Moderate2: LUM-201 PEMs

baseline IGF > 30 ng/ml and stim

GH ≥ 5 ng/ml

Conclusions

13

Significant Prior Clinical Experience with LUM-201 – Both Pediatric and Adult

• Multiple trials were conducted by Merck prior to Lumos acquisition of LUM-201 in July 2018

• Six large-scale adult studies (n ~1,000)

o In every adult indication, IGF-1 and/or GH levels were meaningfully increased from baseline by LUM-201 treatment

• Three clinical trials in pediatric patients (n ~200)

o Phase 1 Study 019 – Pharmacokinetics/Pharmacodynamics

o Phase 2 Study 020 – Patients naïve to treatment

o Phase 2 Study 024 – Patients previously treated with rhGH

• No significant safety concerns were identified in any of the studies

Lumos conducted post-hoc analysis of Study 020

o Established definition of “PEM-positive” patients as those with a functional but reduced HP-GH axis

o Revealed striking efficacy differential in PEM-positive patients, that will serve as basis for future trials

o Data strongly support potential for improved efficacy at higher doses

o Analysis generated IP for use of LUM-201 in PGHD and other growth hormone deficiency indications

14

Study 020 Post-Hoc Analysis: PEM-Positive Patients Responsive to LUM-201

• Naïve PGHD, Study 020

o N=68; three arms

o Placebo patients switched to rhGH at

6 months

o Annualized growth shown for each arm

• PEM-positive subset:

o LUM-201 0.8 mg/kg not statistically

different from rhGH

o Dose response: 0.8 mg/kg statistically

superior to 0.4 mg/kg

PEM = Predictive Enrichment Marker

1 Bright 2021 JES

All Subjects PEM-Negative PEM-Positive

mg/kg

LUM-201

mg/kg

LUM-201

mg/kg

LUM-201

p<0.0001 p<0.0001

p=0.082

p=0.016

Expect prospective inclusion of only PEM(+) patients and higher doses to improve response to LUM-201

1

15

PK/PD: Evidence of a PK and PD Dose Response in Healthy Volunteers

PharmacodynamicsPharmacokinetics

Dose response to 5.6 mg/kg PGHD

dose equivalent*

PD plateau possible ≥ 2.8 mg/kg PGHD

dose equivalent*

Higher LUM-201 doses produce higher plasma concentrations of LUM-201 & GH up to PD plateau

PD curve shows potential for LUM-201 doses in OraGrowtH210 Trial to produce greater GH response

Merck Study 001 in healthy adult subjects, results based on single LUM-201 dose administered *Dose equivalence is based on AUC

16

GH Response to LUM-201 in Healthy Volunteers and PGHD Patients

Dose equivalence is based on AUC.

Study 001 - Healthy adult subjects

Study 008 - Healthy adult subjects

PEM+ PGHD Cmax values lie on the curve

Anticipate 3.2 mg/kg to produce maximal pharmacodynamic effect

Study 020 – PEM-positive PGHD

Growth hormone Cmax in response to single doses of LUM-201 in healthy adults can serve as a benchmark

17

OraGrowtH210 Trial: Phase 2 Trial in 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 • n = 80

• PEM(+) PGHD subjects

• Inclusion: stim GH ≥ 5

ng/ml and baseline

IGF-1 >30 ng/ml

• rhGH treatment naïve

• ~40 trial sites US &

International

• Trial opened Q4 2020

Primary Endpoint:

• Annualized Height

Velocity (AHV)

Goals:

• Prospectively confirm

utility of PEM strategy

• Determine optimal

dose for Phase 3

Interim AHV and safety data on 40 subjects at 6 months on therapy anticipated by end of 2022

Primary outcome data for OraGrowtH210 Trial on 80 subjects 2H2023

Interim Data Analysis (n = 40) – at 6 months

Primary Outcome Data (n = 80) – at 6 months

Total Study Duration – 12 months

Objectives

TreatmentRandomizationScreening

R

18

PK/PD Data Show LUM-201 Pulsatile MOA & Potential Efficacy in PGHD Patients

Merck Study 020 patient subset. Cassorla, F.

PEM Positive PEM Negative

Patient A Patient B Patient C

Baseline 6months Baseline 6months Baseline 6months

IGF-1(ng/ml)

182 231 53 72 17 15

Q20m

24h GH

Mean(ng/ml)

3.4 6.3 1.0 1.3 0.5 0.3

AUC(ng*hr/ml)

75.5 137.3 17.6 25.0 4.9 3.4

Height

Velocity

(cm/yr)

3.7 7.9 3.5 8.9 1.1 1.8

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240

6

12

18

24

30

Sampling Time (hr)

Seru

m G

row

th H

orm

on

e (

ng

/ml)

Patient A

Baseline 6 months

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240.0

0.2

0.4

0.6

0.8

1.0

1.2

Sampling Time (hr)

Seru

m G

row

th H

orm

on

e (

ng

/ml)

Patient C

Baseline 6 months

PEM-Positive Patient A

PEM-Negative Patient C

PGHD patients administered 0.8 mg/kg/day LUM-201 for 6 months

19

• n = up to 24

• Open-label study

• PGHD patients

• rhGH-treatment naïve

• 12-month dosing

• Single, specialized

clinical site

• Q10 minute GH

sampling for 12 hours

OraGrowtH212 Trial: Pharmacokinetic / Pharmacodynamic Trial in PGHD

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

Interim AHV and safety data on 10 subjects anticipated by end of 2022

Objectives

n = up to 12 - LUM-201: 3.2 mg/kg/day

n = up to 12 - LUM-201: 1.6 mg/kg/day

R

TreatmentRandomizationScreening

Interim Data Analysis (n =10) – at 6 months

Primary Outcome Data (n = up to 24) – at 6 months


20

• n = up to 20

• PGHD subjects from

rhGH treatment arm of

OraGrowtH210 Trial

after completion of 12

months on therapy

• Open-label, multi-center

switch study

• LUM-201 treatment

months 13-24

OraGrowtH213 Trial: Phase 2 Switch Trial in PGHD

Primary Objectives:

• Assess growth and safety of

oral LUM-201 following 12

months of daily injections

of rhGH

Switch study initiated

Objectives

n = up to 20 – LUM-201 at dose level of 3.2 mg/kg/day


21

Exclusivity and Barriers with Orphan Designation and IP

• Orphan Drug Designation received in US and EU for GHD in 2017

o With potential pediatric extensions, eligible for 12 years exclusivity in EU and 7.5 years in US

o Plan to seek designation in Japan

• Intellectual Property

o “Detecting and Treating Growth Hormone Deficiency"

• Use of LUM-201 in PGHD and other GHD indications

• US patent issued with expiration in 2036

• Patent applications filed in multiple other countries

22

Secure Cash Position

Cash balance to support current operations through primary outcome data readouts for

OraGrowtH210 and OraGrowtH212 Trials

Metric Position

Cash balance December 31, 2021 $94.8 million

Cash use through 2022 $8.5 to $9.5 million per quarter

Strong financial positionCash runway through primary outcome data for OraGrowtH210 and OraGrowtH212 Trials

Shares outstanding as of December 31, 2021 8,357,391

23

Investment Highlights

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

• Prior data support potential efficacy and safety of LUM-201 across multiple indications

• Potential to disrupt significant subset of sizable injectable market for GHD

• Worldwide market for GHD disorders is $3.4 billion*

• Market for initial oral LUM-201 indication, PGHD, is $1.2 billion*

• Cash balance of $94.8 million at close of Q4 2021

• Cash runway through primary outcome data for OraGrowtH210 & OraGrowtH212 Trials

Late-stage

Trials in PGHD

• OraGrowtH210 Trial (Phase 2):

• OraGrowtH212 Trial (PK/PD):

• OraGrowtH213 Trial (Switch):

Interim data by year-end 2022 | Primary data 2H2023

Interim data by year-end 2022

Initiated

24

Supplemental Materials

25

Total Core Growth Hormone Market approaching $8B with PGHD the largest market

$-

$0.5

$1.0

$1.5

$2.0

$2.5

2019 2020 2021 2022 2023 2024 2025 2026

Pro

jec

ted

WW

Re

ve

nu

e (

US

$ B

)

PGHD

Adult GHD

Turner

ISS

PWS

SGA

Others

Global HGH Market Projections*

2026 Share

CAGR

100% 7.9%

27% 7.9%

22% 8.9%

19% 8.0%

17% 6.9%

6% 6.3%

6% 8.3%

3% 7.8%

By Condition By Region

Source: Grand View Research, “Human Growth Hormone (HGH) Market Analysis and Segment Forecast to 2026”, 2019; Triangle Insights, Sep 2020; FDA; WHO; Industry Journals; Investor Presentations; GlobalData

* NOTE: Pre-Covid projections** Includes Creutzfeldt–Jakob disease, chronic kidney disease, and SHOX gene haploinsufficiency

**1.97

3.40

$1.07

$2.09

$0.60

$0.32

$0.95

$2.00

$4.59

$7.81

$-

$1

$2

$3

$4

$5

$6

$7

$8

$9

2019 2026

Pro

jecte

d W

W R

even

ue (

US

$ B

)

RoW

Japan

EU

US

21%

13%

23%

43%

25%

4%

27%

44%

26

23%

44%

33%

Poor Compliance with Injectables Leads to Suboptimal Real-World Outcomes

1 Rosenfeld 2008 Endocrine Practice (adapted) 2 Cutfield 2011 PLOS ONE (adapted)

64-77% are non-compliant1 Significantly reduced height velocity2

36%

23%

41%

Highly compliant

Occasionally non-compliant

Non-compliant and skeptical

Parents of children

(age 4-12)

Teens

(age 13-17)

Poor compliance leads to suboptimal growth

p<0.01

p<0.001

27

Severity of PGHD Affects Treatment Response

SDS Standard Deviation Score 1 Blum 2021 JES; mean growth after 1 year of treatment 2 Bright 2021 JES; mean annualized growth after 6 months of treatment in 68 patients

Severe

38%

Moderate

62%

GeNeSIS1

12,315 GHD

514 isolated GHD

Moderate

51%

Severe

49%

020 Trial2

79 PGHD

BaselineChronological age (y) 6.80 7.10 9.1 9.9

Height SDS -3.01 -2.58 -2.6 -4.6

rhGHHeight velocity (cm/y) 9.62 8.29 8.8* 14.0


LUM-201 0.8

mg/kg

Height velocity (cm/y) 7.7* 5.4

020 data corroborated by large database

• Segmentation achieved using IGF-1 and

peak GH to stimulation tests

• A large proportion of patients are moderate

• Severe grow faster on rhGH than moderate

Moderate patients grow similarly on rhGH

and LUM-201

Conclusions

* Not statistically different in same study

28

Importance of Pulsatility in Growth Hormone Release

• Physiological release of GH is pulsatile

• The unique basis of LUM-201 therapeutic intervention is to increase the amplitude of pulsatile GH secretion

Limited

GH Release

Very Limited/Null

GH Release

Normal

GH Release

Spectrum of Pediatric Growth Hormone Release

29

GH Pulsatility and Connection to Growth

• Challenging to answer

o Higher doses of rhGH do increase growth in PGHD patients

o Difficult to directly compare continuous vs pulsatile dosing in patients without using a GHSR1a agonist

• In adults with GHD and healthy elderly, and in a subset of PGHD patients from Merck Study 020, treatment

with LUM-201 for up to one year increases the amplitude of GH released in endogenous pulses

• Evidence supports potential for improved growth with pulsatile GH

o Experiments in rats show pulsatile dosing of GH promotes more growth than continuous dosing1

o Higher frequency of rhGH dosing has been shown to promote more growth than less frequent dosing in PGHD2

1 Gevers 1996 Endocrinol 2 MacGillivray 1996 J Clin Endocrinol Metab

30

• Dwarf rats treated with continuous, pulsatile or combination rhGH for 7 days

Pulsatility of GH Release is Important to Growth in Dwarf Rats

Gevers 1996 Endocrinol (adapted)

C P C P 28% P

72% C

72% P

28% C

C = continuous

P = pulsatile

144 ug/day

total dose

200 ug/day

total dose

Pulsatile administration of rhGH that mimics natural secretion of GH is more effective

in stimulating growth than continuous administration

31

Increasing Frequency of rhGH Administration Improves Growth

• PGHD

• Same total weekly dose of rhGH: 0.3 mg/kg/week

MacGillivray 1996 J Clin Endocrinol Metab

Shaded area

represents two

standard deviation

scores (SDS) from

normal height

Higher frequency of rhGH administration in PGHD is more effective in stimulating

growth than less frequent administration

32

More GH Released from LUM-201 Stim than from Standard Stim Test Agents

0 2 4 6 8 10 12

GH to Standard GH Stimulation Tests (ng/mL)

2

4

6

8

20

40

60

80

GH

to S

ingle

Dose L

UM

-201 (

ng/m

L)

68 children with growth hormone deficiency

All had 2 standard GH stimulation tests• Standard test agents: arginine, clonidine,

l-dopa, glucagon, insulin

All had a single dose of LUM-201 stim test

Data presented at the 2021 Annual Meeting of The Endocrine Society

33

LUM-201 Augments Pulsatility

• Adults with GH deficiency

• Individual subjects

• Representative 24-hour GH profiles on Day 4 of treatment

Chapman 1997 J Clin Endocrinol

Baseline

10 mg, Day 4

50 mg, Day 4

34

LUM-201 Augments Pulsatility in GHD Adults

• LUM-201 augments endogenous GH pulses

• rhGH is administered as single, daily bolus doses

1 Adapted, Chapman 1997 J Clin Endocrinol 2 Janssen 1999 Br J Clin Pharmacol (Genotropin)

24h GH profile following oral LUM-201

administration in an adult with GH deficiency1

24h PK profile following subcutaneous rhGH

injection in adults with GH deficiency2

0.6 IU

1.8 IU

1.2 IU

GH

(m

UI-1

)

0

2

4

6

Time

Seru

m G

H (

ug

/L)

22:00 2:00 6:00 10:00 14:00 18:00 22:00

10 mg LUM-201, Day 4

50 mg LUM-201, Day 4

Baseline

17-year old male Mean GH (ug/L) IGF-1 (ug/L)Baseline: 0.560 16410 mg: 0.861 16950 mg: 1.000 249

Potential to achieve non-inferior growth from smaller GH AUC via

LUM-201 pulsatile delivery vs rhGH bolus administration

35

• Patients A & B = PEM-Positive

o Baseline IGF-1 > 30 ng/mL and peak GH to single LUM-201 dose ≥ 5 ng/mL*

o LUM-201 treatment augmented pulsatile GH secretion in PEM-Positive patients

o Less than 2-fold increase in GH secretion produced substantial increase in height velocity

• Patient C = PEM-Negative

o Baseline IGF-1 ≤ 30 ng/mL and peak GH to single LUM-201 dose < 5 ng/mL*

o As expected, no increase in pulsatile GH secretion or height velocity observed on LUM-201

* IGF-I and peak GH cutoffs determined by Receiver Operating Characteristic analyses in 24 PGHD subjects treated with 0.8 mg/kg/day

LUM-201; Bright G and Blum W JES 2021

LUM-201 augments pulsatile GH release, causing substantial height velocity increase in PEM+ patients

PEM Status Reflects LUM-201 Effect on Pulsatile GH Secretion & HV Response


Analysis of Subset of PGHD Patients from Merck 020 Trial

36

Baseline Data and PEM Status for Subset of PGHD Patients from Merck 020 Trial

* Highest acute GH response to a single 0.8 mg/kg LUM-201 dose. Merck Study 020 patient subset. Cassorla, F.

LUM-201 0.8 mg/kg/day

Subject Sex

Screening/Baseline

Age

(yrs)

Height

velocity

(cm/yr)

Standard GH

stimulation tests

(ng/mL)

Peak GH to single

LUM-201 dose*

(ng/mL)

IGF-1

(ng/mL)

PEM

Status

A M 11.9 3.7 8.3 102 182 +

B M 9.5 3.5 1.9 5.0 53 +

C M 11.8 1.1 1.3 1.9 17 —

Screening

Standard GH

stimulation tests

Peak GH to single

LUM-201 dose*

Baseline

Height

IGF-1

Q20m 24h GH

6 months

Height

IGF-1

Q20m 24h GH

37

HP-GH Axis Responsive to LUM-201: Patient A

Baseline

6 months

LUM-201

0.8 mg/kg/d

IGF-1 (ng/ml) 182 231

Q20m

24h GH

Mean (ng/ml) 3.4 6.3

AUC (ng*hr/ml) 75.5 137.3

Height velocity (cm/yr) 3.7 7.9

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240

6

12

18

24

30

Sampling Time (hr)

Seru

m G

row

th H

orm

on

e (

ng

/ml)

Patient A

Baseline 6 months


Q20m

24h GH

PEM+ patient: LUM-201 augments pulsatile GH secretion resulting in substantial increase in height velocity

Once daily dosing of LUM-201 sufficient to augment pulses throughout a 24-hour period

PEM-Positive Patient


38

HP-GH Axis Responsive to LUM-201: Patient B

Baseline

6 months

LUM-201

0.8 mg/kg/d

IGF-1 (ng/ml) 53 72

Q20m

24h GH


AUC (ng*hr/ml) 17.6 25.0


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240.0

0.5

1.0

1.5

2.0

2.5

3.0

Sampling Time (hr)

Seru

m G

row

th H

orm

on

e (

ng

/ml)

Patient B

Baseline 6 months

Q20m

24h GH

PEM-Positive Patient



PEM+ patient: LUM-201 augments pulsatile GH secretion resulting in substantial increase in height velocity

Once daily dosing of LUM-201 sufficient to augment pulses throughout a 24-hour period

39

HP-GH Axis Not Responsive to LUM-201: Patient C

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240.0

0.2

0.4

0.6

0.8

1.0

1.2

Sampling Time (hr)

Seru

m G

row

th H

orm

on

e (

ng

/ml)

Patient C

Baseline 6 months

Baseline

6 months

LUM-201

0.8 mg/kg/d

IGF-1 (ng/ml) 17 15

Q20m

24h GH


AUC (ng*hr/ml) 4.9 3.4


Q20m

24h GH

PEM ( ) patient: No change in pulsatile GH secretion or height velocity on LUM-201 as expected

PEM-Negative Patient



40

LUM-201 Effects Are Durable In Healthy Elderly

Nass 2008 Ann Intern Med

LUM-201 mediated increases in serum GH and IGF-1 are sustained over 1 year of treatment

41

LUM-201 Deal Terms

*Milestone figures are maximum, may be less depending on development stage achieved and total net sales up to $1B

PartnerUpfront

PaymentDevelopment Milestones*

Sales Milestones*

Worldwide

Sales Royalties,

Combined

Ammonett $3.5M$17M first indication

$14M second indication$55M

Merck N/A$14M first indication

$8.5M second indication$80M

10% to 12%,

subject to

standard generic

erosion reductions

Documents

Therapeutics For Rare Diseases - Lumos Pharma