Company Overview. January 2021

(1)

Company Overview

(2)

Legal Disclaimer

This Presentation contains forward-looking statements and information within the meaning of the Private Securities Litigation Reform Act of 1995 relating to our current and future prospects and our operations and financial results, which are based on currently available information. All statements other than statements of historical facts contained in this Presentation, including express or implied statements regarding our strategy, future financial condition, future operations, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as ‘‘aim,’’

‘‘anticipate,’’ ‘‘assume,’’ ‘‘believe,’’ ‘‘contemplate,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘design,’’ ‘‘due,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘goal,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘objective,’’ ‘‘plan,’’ ‘‘predict,’’

‘‘positioned,’’ ‘‘potential,’’ ‘‘seek,’’ ‘‘should,’’ ‘‘target,’’ ‘‘will,’’ ‘‘would’’ and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. These forward-looking statements include statements about the initiation, timing, progress and results of our current and future clinical trials and current and future preclinical studies of our product candidates, including our clinical trials of FT-4202 for the treatment of sickle cell disease, or SCD, and our clinical trials of FT-7051 for the treatment of metastatic castration-resistant prostate cancer, or mCRPC, and of our research and development programs; our plans to develop and commercialize our current product candidates and any future product candidates; risks related to the competitive landscape; the implementation of our business model and strategic plans for our business, current product candidates and any future product candidates; and the potential impact of COVID-19 on strategy, our employees, supply chain, future operations and clinical trials. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward- looking statements.

Any forward looking statements in this presentation are based on management's current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and

uncertainties include, but are not limited to: uncertainties related to the initiation and conduct of studies and other development requirements for our product candidates; the risk that any one or more of Forma's product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies will not be predictive of future results in connection with future studies; risks related to Forma's ability to protect and maintain our intellectual property position; and risks related to the ability of our licensors to protect and maintain their intellectual property position. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Forma's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in Forma's most recent

quarterly reports on Form10-Q filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Forma's other filings with the Securities and Exchange Commission. All information in this presentation is as of the date of the release,and Forma undertakes no duty to update this information unless required by law.

(3)

Transforming the lives of patients with rare

hematologic diseases and cancers

(4)

• Developing three NCE’s spanning rare hematological disease, and both hematological and

solid tumor oncology

• FT-4202 represents a potential foundational disease-modifying therapy for SCD with data

supporting tolerability and proof of concept in SCD patients

• Olutasidenib (FT-2102) has generated positive registrational results in relapsed/refractory

AML patients with an IDH1 mutation, and encouraging 12 month results in glioma patients

• FT-7051 Phase 1 trial in mCRPC open for enrollment with potential to address prostate

cancer cell resistance related to molecular alterations in AR, including AR-v7

• Strong IP position with over 40 patent families overall, including patent protection through

2038 (earliest) for core programs

• Strong cash position: $384M as of 9/30/20, approximately $276M gross proceeds from

December 2020 follow on offering

• Key pipeline milestones expected throughout 2021 and 2022

Key investment highlights

(5)

Strong progress throughout 2020

FT-4202

300mg MAD1,

POC in SCD pts.

600mg MAD2

enrolling

Olutasidenib

(FT-2102)

completed

Ph 2 IA2 in

R/R AML pts.

FT-4202

completed Ph.1

single 700mg

dose in SCD

patients

✓

Series D

✓

BD strategy

1

✓

IPO

FT-4202

received FDA

designations

FT-7051 IND

clearance

(6)

Frank Lee

President, Chief Executive Officer, and Director

SVP, Global Product Strategy and Therapeutic Head for Immunology, Ophthalmology and Infectious Disease, Genentech

David Cook, Ph.D.

SVP, Chief Scientific Officer

EVP and Chief Scientific Officer, Seres Therapeutics COO, International AIDS Vaccine Initiative

SVP, Cerus

Patrick Kelly, M.D. SVP, Chief Medical Officer

Senior Medical Director of Early Development, Takeda Oncology VP of Clinical Development, Infinity Pharmaceuticals

Faculty, St. Jude Children’s Research Hospital and Cincinnati Children’s Hospital

Jeannette Potts, Ph.D.

SVP, General Counsel and Corporate Secretary

VP, Head Counsel, Research and Development, Takeda Pharmaceuticals

VP, Global R&D Legal Practice Group, Takeda

Todd Shegog

SVP, Chief Financial Officer

CFO, Synlogic

SVP and CFO, FORUM Pharmaceuticals

SVP, Finance and CFO, Millennium Pharmaceuticals; Takeda Oncology

Mary Wadlinger

SVP, Corporate Affairs and Chief Human Resources Officer

VP, Human Resources, Millennium Pharmaceuticals; Takeda Oncology

Leadership team brings global development and commercial

execution experience

Board of Directors

Peter Wirth, J.D.

Chairman of the Board of Directors

Timothy P. Clackson, Ph.D. Director Marsha Fanucci Director Wayne Frederick, M.D. Director Peter Kolchinsky, Ph.D. Director Paolo Paoletti, M.D. Director Tom Wiggans Director

Selwyn M. Vickers, M.D., F.A.C.S.

(7)

Forma Therapeutics’ pipeline

Program

(Targets) Indication

Development Stage

Commercial Rights Recent and expected events

Preclinical Phase 1 Phase 2 Phase 3

FT-4202 (PKR) Sickle Cell Disease

◼ Presented Ph.1 SCD data at

EHA/ASH

◼ Complete Phase 1 SCD MAD/OLE ◼ Initiate Phase 2/3 pivotal trial FT-7051

(CBP/p300)

mCRPC

(AR Resistant)

◼ IND cleared

◼ Initiate Phase 1 trial

Olutasidenib (FT-2102) (IDH1m)

AML ◼ NDA-enabling Phase 2 IA2

completed in R/R AML

Glioma ◼ Phase 1 trial, 12-month data _{presented at ASCO 2020}

FT-8225 (FASN) NASH CC-95775 (BET) NHL B1-1701963

(KRAS) Solid Tumors

(8)

Forma’s development programs

PKR

Sickle cell

disease

IDH1

AML and Glioma

Partnering

FASN

NASH

Partnering

CBP/

p300

Prostate cancer

(9)

Significant unmet needs remain in sickle cell disease

Sources: Evaluate Report Sickle cell disease by country accessed February 03, 2020. Smith WR, et al. Ann Intern Med. 2008;148:94–101. Lanzkron S, et

❑

Improvement in BOTH hemoglobin and

vaso-occlusive crises

❑

Treatment that is safe to

be administered early in life

❑

Convenient, self-administered therapy

❑

Low risk of adverse events and

drug-drug interactions

Reduction in

average life

expectancy

25-30yr

SCD patients in

the US

~100K

Days with pain

~55%

SCD Overview

What's Needed?

Stroke, Acute Chest

Syndrome, Renal

failure

Risk of

(10)

10

Treatment options for SCD

Chronic Transfusions L-Glutamine (Endari®)

Non-curative Treatments

Transplant (HSCT) Voxelotor (Oxbryta®) Crizanlizumab (Adakveo®)

Curative Treatment

Hydroxyurea (HU)

Standard of Care

(Non-curative) Treatments

Opioids

SCD

Treatment

Options

On-market ~2 vs 3 VOCs/yr treated vs placebo Gene Therapy + SCT In development ~50% of patients ≥1g/dL HbS

(11)

✓

Both anemia and VOCs

✓

Multi-modal MoA: decreases 2,3 DPG and increases ATP

✓

No aromatase inhibition properties

✓

Oral, once daily tablet

✓

Low risk of drug-drug interactions

✓

Does not autoinduce its own metabolism

(12)

FT-4202, Randomized multi-centered placebo controlled Phase 1

study informs pivotal Phase 2/3

2020

Phase 1 Healthy

Volunteer Study

Proof of mechanism confirmed

FDA Fast Track,

Rare Pediatric, Orphan Drug

Designations Granted

Phase 1 SCD

700mg

Single Dose

Phase 2/3 SCD

Registration Program

200/400 mg

Phase 1 SCD

300mg

MAD1, 14days

Phase 1 SCD

600mg

MAD2, 14 days

Phase 1 SCD

Open Label Ext.

12 weeks

400 mg

(13)

Sickle cell disease overview

SCD is characterized by a point mutation HbS,

which upon deoxygenation polymerizes to

cause a sickle-shaped RBC

Sickle-RBCs block blood flow causing VOCs,

and sickling process damages RBCs leading to

hemolysis and anemia

Source: Figures adapted from Steinberg, M.H. TheScientificWorldJOURNAL (2008) 8, 1295–1324 ISSN 1537-744X; DOI 10.1100/tsw.2008.157

Abnormal, sickled RBCs (sickle cells)

Sickle cells blocking blood flow

Sticky sickle cells

Cross-section of sickle cell

Abnormal hemoglobin form strands that cause sickle shape

α

β

A

β

S

α

β

A

β

S

Normal

(HbA)

Abnormal

(HbS)

-Pro-Glu-Glu-

-Pro-

Val

-Glu-α

α

β

+O

₂

−

O

₂

+O

₂

−

O

₂

(14)

The biologic effects of

↑

2,3-DPG and

↓

ATP in sickle RBCs:

VOCs and Anemia

SCD RBCs have more 2,3-DPG & less ATP

than healthy RBCs

Note: *, p<0.05. Mann-Whitney non-parametric test used to determine statistical differences between the groups Source: Forma internal data

↑

2,3-DPG

HbS

HbA

• Increased levels of 2,3-DPG, resulting in decreased

hemoglobin oxygen (O

₂

) affinity (i.e., increased P

₅₀

)

• Decreased levels of ATP, leading to insufficient energy

for membrane maintenance and repair

Increased 2,3-DPG and decreased ATP

exacerbate SCD pathogenesis

HV SCD

2,3-DPG

HV SCD

(15)

GLUCOSE Hb Deoxy -Hb PYRUVATE ATP ADP PEP 2,3-DPG PKR FT-4202 HbS polymerization RBC membrane integrity

ANTICIPATED CLINICAL OUTCOMES:

Increased Hb levels Decreased vaso-occlusion

HYPOTHESIS #2:

PKR activation increases ATP, promoting RBC repair/health and

reducing hemolysis

HYPOTHESIS #1:

PKR activation decreases 2,3-DPG, reducing HbS polymerization

and sickling

Activating PKR is expected to

↓

2,3-DPG and

↑

ATP in HbS RBCs:

(16)

Ongoing Phase 1 Trial for FT-4202: A randomized,

placebo-controlled, multi-center trial

0 100 200 300 400 500 600 200 400 600 Dose (mg QD) S te a d y S ta te P D B io m a rk e r (  g /m L ) 2,3-DPG ATP line: median

shaded area: 5th-95th range

Healthy Volunteers

• Randomization 6:2 vs. placebo • Dose range 200 mg to 1000 mg

evaluated

Single Ascending Dose (Completed)

• Randomization 9:3 vs. placebo • 14 days treatment

• Doses 100 mg-300 mg BID & 400 mg QD evaluated

Multiple Ascending Dose (Completed) Kalfa et al. ASH 2019

• Safety

• PK/PD relationship

(17)

Ongoing Phase 1 Trial for FT-4202: A randomized,

placebo-controlled, multi-center trial

• Block Randomization of 7:2 or 9:3 vs. placebo

• 14 days treatment

12-week Cohort (enrolling)

• 400 mg daily

o Open-label

o Define safety

o Additional Insights in PK/PD, biology, organ systems

Roll-over

ASH 2020: MAD 1 (n = 9)

• 300 mg X 14 days

o Safety

o PK/PD

o Insights into biologic effects

• Confirmed Phase 2 Doses

Multiple Ascending Dose in Patients with SCD (Enrolling) • Randomization 5:2 vs. placebo

• Single 700 mg dose completed Estepp et al. EHA 2020

• Safety

• Comparable PK

• PKR enzyme responsive to FT-4202 activation

Single Dose in Patients with SCD

MAD 2 (enrolling)

• 600 mg X 14 days

o Define safety margin

o Additional insights into PK/PD, biology 0 100 200 300 400 500 600 200 400 600 Dose (mg QD) S te a d y S ta te P D B io m a rk e r (  g /m L ) 2,3-DPG ATP line: median

shaded area: 5th-95th range

Healthy Volunteers

• Randomization 6:2 vs. placebo • Dose range 200 mg to 1000 mg

evaluated

Single Ascending Dose (Completed)

• Randomization 9:3 vs. placebo • 14 days treatment

• Doses 100 mg-300 mg BID & 400 mg QD evaluated

Multiple Ascending Dose (Completed) Kalfa et al. ASH 2019

• Safety

• PK/PD relationship

(18)

FT-4202 Updated MAD 1 Data

(19)

FT-4202 as a potential foundational therapy: Beyond

hemoglobin improvement

✓

6 of 7

achieved a > 1 g/dL increase in hemoglobin (Hb);

median 1.2 g/dL increase (range 0, 2.3 g/dL);

o

Among responders, a mean 1.6 g/dL increase

✓

7 of 7

achieved a reduction in reticulocytes; median

60% decrease (range -39%, -81%);

✓

6 of 7

achieved a reduction in lactate dehydrogenase

(LDH); median 36% decrease (range +18%, -57%); and

✓

7 of 7

achieved a reduction in bilirubin; median 35%

decrease (range -7%, -63%).

✓

Healthier RBCs

–

shift toward normalization on

deformability (Oxygenscan and Osmoscan)

Anemia - fatigue

• Low hemoglobin

• High % reticulocytes

Hemolysis - oxidative

and inflammation

• High LDH

• High bilirubin

Sickle RBC’s

• Stiff and unhealthy

• Short lifespan

FT-4202

(20)

Treatment-emergent adverse events (TEAEs):

Adverse events (AEs) after start of study treatment

FT-4202 300 mg daily

X 14 days

(N = 7)

Placebo daily

X 14 days

(N = 2)

Any TEAE, n (%)

6 (86%)

1 (50)

Related to study drug, n (%)

2 (29%)

0 Serious adverse events (SAE), n (%)

0

• SCD MAD 1 Cohor

t (n=9): Eighteen TEAEs were reported in 7 patients

o

FT-4202 cohort (11 TEAEs): Six Grade 1 and five Grade 2 AEs reported in 6 patients

−

Two possibly related AEs (Grade 1 headache and Grade 1 nausea) occurred in 1 patient each

−

All five Grade 2 AEs considered unrelated

• 3 uncomplicated sickle pain events (in 2 patients) and 1 event each of nausea/vomiting (in 1 patient)

o

Placebo cohort (7 TEAEs): Three Grade 1, two Grade 2, one Grade 3 and one Grade 4 AEs occurred in 1 patient

−

All AEs considered unrelated to treatment (disease under study and/or strenuous exercise)

• Increased AST (Grade 1 and 2), increased LDH (Grade 1), and increased creatinine kinase (Grade 2, 3, and 4)

Unblinded analysis: FT-4202 is well-tolerated in patients with SCD

(21)

PK of FT-4202 comparable in HVs and patients with SCD:

Pharmacodynamics support once-daily dosing

PK/PD of the 300 mg SCD MAD Cohort supports the dose range of 200 mg to 400 mg of

FT-4202 once daily for the planned Phase 2/3 study

FT-4202 PK in HV

and Patients with SCD

2,3-DPG profile

in SCD RBCs

ATP profile

in SCD RBCs

0 4 8 12 16 20 24 0 20 40 60 Time (Day) A T P (% C h a n g e f ro m B a s e li n e ) 700 mg SAD 300 mg QD MAD 0 4 8 12 16 20 24 -40 -20 0 20 Time (Day) 2 ,3 -D P G (% C h a n g e f ro m B a s e li n e ) 700 mg SAD 300 mg QD MAD

(22)

22 2000 4000 6000 8000 15 20 25 30 35 2,3-DPG (g/gHb) P5 0 (m m H g ) HV Pre-dose Healthy Volunteer r2=0.68 SCD Post-dose SCD Pre-dose HV Post-dose

• SCD RBC’s have higher P

₅₀

at baseline compared

to HV RBCs

• Normal P

₅₀

values observed in SCD RBCs 24-hrs

after a single dose or after 14-days of FT-4202

• Change in oxygen

affinity correlates with

2,3-DPG response

• HbS oxygen affinity

appears more sensitive

to 2,3-DPG levels

FT-4202 increases oxygen affinity in both HV and sickle RBCs

Placebo 700 mg Placebo 700 mg Untreated Treated

15 20 25 30 35 P5 0 (m m H g )

Pre-Dose 24 h Post Dose ns

**

** ns

HV SAD SCD SAD SCD MAD#

* _ns

*P=0.063; **P=0.031

#

_{Based on FT-4202 PK analysis, n=9}

(23)

Patient with SCD before and after a single dose of FT-4202 (700 mg)

0 50 100 150 200 250 300 350 400 450 500 0.0 0.2 0.4 0.6 Osmolality (mOsm/kg) E lo n g a ti o n I n d e x Pre Post O_min 108 115 O_hyper 380 400 Healthy RBCs SCD RBCs

Osmoscan

Improved osmolality-dependent membrane

function

post

dose

0 20 40 60 80 100 120 140 0.0 0.2 0.4 0.6 pO2 (mmHg) E lo n g a ti o n I n d e x Pre Post POS (mm Hg) 32 ( ) 18 ( ) EI_min 0.19 0.32 Healthy RBCs SCD RBCs

Oxygenscan

Improved O

₂

-dependent change in

deformability

post

dose

0 50 100 150 0 25 50 75 100 pO2 (mmHg) % O x y h e m o g lo b in Pre Post P₅₀(mm Hg) 32 26 POS (mm Hg) 32( ) 18( ) SCD RBCs Healthy RBCs

Oxygen Affinity

Increased oxygen affinity

post

dose

Healthy RBC:

---

SCD RBC (pre): --- SCD RBC (post):

(24)

24

Daily FT-

4202 improves sickle RBCs’ functional health

↓2,3

-DPG

Normalizes Oxygen Affinity

↓2,3

-DPG

↓

HbS polymerization =

↓ POS

Improved deformability over baseline

↑ATP

Improved RBC membrane function

Improved deformability over baseline

Oxygen Affinity Curve

Oxygenscan

Osmoscan

Pre EOT P50 29.7 25.2 Pre EOT POS Ei_max 40.6 30.7 0.32 0.52

**Patient with SCD* prior to and after 14 days of daily 300 mg FT-4202**

Healthy RBC:

---

SCD RBC (pre):

---

SCD RBC EOT (Day 15):

---Pre EOT Eimax 0.42 0.54

POS = point of sickling

0 50 100 150 0 25 50 75 100 pO₂ (mmHg) % O x y h e m o g lo b in 0 50 100 150 200 250 300 350 400 450 500 0.0 0.2 0.4 0.6 Osmolality (mOsm/kg) E lo n g a ti o n I n d e x 0 20 40 60 80 100 120 140 0.0 0.2 0.4 0.6 pO₂ (mmHg) E lo n g a ti o n I n d e x

(25)

Improved sickle RBC health and function can persist after

FT-4202 treatment

0 50 100 150 0 25 50 75 100 pO₂ (mmHg) % O x y h e m o g lo b in 0 50 100 150 200 250 300 350 400 450 500 0.0 0.2 0.4 0.6 Osmolality (mOsm/kg) E lo n g a ti o n I n d e x

After FT-4202 discontinuation:

Oxygen affinity can return to baseline

After FT-4202 discontinuation:

POS can return to baseline

Improved deformability can persist

After FT-4202 discontinuation:

Improved deformability can persist

Oxygen Affinity Curve

Oxygenscan

Osmoscan

Pre EOT EOS P50 29.7 25.2 32

Pre EOT EOS POS

Ei_max

40.6 30.7 40.8 0.32 0.52 0.49

**Patient with SCD* before, after 14 days of daily 300 mg FT-4202 and after a 7-day wash-out**

Healthy RBC:

---

SCD RBC (pre):

---

SCD RBC EOT (Day 15):

---

SCD RBC EOS (Day 21):

---

-Pre EOT EOS Eimax 0.42 0.54 0.52 0 20 40 60 80 100 120 140 0.0 0.2 0.4 0.6 pO₂ (mmHg) E lo n g a ti o n I n d e x

(26)

Proof of Concept: Improved hematologic and hemolytic

parameters after 14-days of 300 mg FT-4202 once daily

Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 Pt 9 -3 -2 -1 0 1 2 3 -80 -60 -40 -20 0 20 40 60 80 H g b A b s o lu te C h a n g e ( g /d L ) R e tic u lo c y te s (% C h a n g e ) Hemoglobin Reticulocytes Untreated# Treated#

• In patients receiving FT-4202: 6 of 7 had a > 1 g/dL

↑

in hemoglobin and all 7 had

↓

in reticulocytes

• Median 1.2 g/dL Hb increase (range 0, 2.3) and median 60% reticulocyte decrease (range -39%, -81%) over baseline

• In patients receiving FT-4202: 6 of 7 had

↓

in LDH and all 7 had

↓

in total bilirubin

• Median 36% LDH decrease (range +18%, -57%) and median 35% bilirubin decrease (range -7%, -63%) over baseline

Pt 1 Pt 2 Pt 3 Pt 4 Pt 5 Pt 6 Pt 7 Pt 8 Pt 9 -80 -60 -40 -20 0 20 40 60 80 % C h a n g e Untreated# Treated# LDH Bilirubin #

_{Based on FT-4202 PK analysis, n=9}

(27)

Increasing hematologic response throughout the treatment interval

• 6 out of 7 patients receiving FT-4202 achieved > 1

g/dL hemoglobin increase over baseline (D1)

o

Maximum response may not have been reached in all

patients

• Persistent ≥ 0.5 g/dL increase over baseline at the

EOS visit (7-day wash-out) in 4 patients

Screening D1

D7/8

D14/15

(EOT)

D21

(EOS)

7

8

9

10

11

12 H

g

b

(g

/d

L

)

• 7 out of 7 patients receiving FT-4202 demonstrated a

decrease in % reticulocytes below baseline (D1)

• 3 out of 7 patients had % reticulocytes ≤ ULN at the

end of treatment period (EOT)

Median

_Median

Hemoglobin

% Reticulocytes

Screening D1

D7/8

D14/15

(EOT)

D21

(EOS)

0

5

10

15

20 R

e

ti

c

u

lo

c

y

te

s

(

%

)

ULN

(28)

Improving hemolytic responses throughout the treatment interval

• 7 out of 7 patients receiving FT-4202 demonstrated a

reduction in bilirubin levels over baseline

• Maximum effects observed at the end of treatment

period (EOT)

• Decrease persists in some patients through EOS visit

Screening

D1

D7/8

D14/15

(EOT)

D21

(EOS)

0

5

10

15 B

il

ir

u

b

in

(

m

g

/d

L

)

ULN

Screening

D1

D7/8

D14/15

(EOT)

D21

(EOS)

0

200

400

600

800 L

D

H

(

U

/L

)

ULN

• 6 out of 7 patients receiving FT-4202 demonstrated

a reduction in LDH levels over baseline

• Maximum effects observed as early as D7/8 of

treatment

• Decrease persists through EOS visit

Total Bilirubin

LDH

Median

(29)

Patient Profile: HbSS hemolytic anemia responsive to FT-4202

• 19-year-old African-American male with Hgb SS, not on hydroxyurea

• Medical history:

o

In 3 months prior to study, hospitalized for VOC and received PRBC transfusion

• Enrolled in study: Randomized to FT-4202 300 mg daily and received 14-days of study treatment

o

Completed study with no adverse events reported

SCR (D-7) D1 D7/8 D14/15 (EOT) D21 (EOS) 8 9 10 11 12 H g b (g /d L )

Hemoglobin

Retics

LDH

SCR (D-7) D1 D7/8 D14/15 (EOT) D21 (EOS) 0 2 4 6 8 10 R e ti c u lo c y te s ( % ) ULN

Bilirubin

SCR (D-7) D1 D7/8 D14/15 (EOT) D21 (EOS) 0 5 10 15 T o ta l B il ir u b in (m g /d L ) ULN SCR (D-7) D1 D7/8 D14/15 (EOT) D21 (EOS) 0 100 200 300 400 500 L D H (U /L ) ULN

• Hemoglobin increased > 2 g/dL

over baseline (D1) at end of

FT-4202 treatment

• Reticulocytes reduced to < ULN

• Reduction in hemolytic

parameters

o

LDH reduced to < ULN

• Biologic effects persisting after

discontinuation of FT-4202

EOT = end of 300 mg FT-4202 daily treatment EOS = end of study

(30)

Conclusions

• FT-4202 has a favorable tolerability profile in patients with SCD

• FT-4202

↓

2,3-DPG and

↑

ATP, resulting in improved RBC functional studies:

o

Normalizes HbS oxygen affinity curve to a HbA affinity curve

o

I

mproves RBC deformability across an oxygen and osmolality gradient

• Improved deformability observed in some patients up to 7-days post daily FT-4202 treatment

• Proof of concept demonstrated with FT-4202 daily for 14 days

o

PKR activation

↑

hemoglobin > 1 gm/dL in 6/7 patients and 7/7 had

↓

reticulocytes and

↓

hemolysis

• Median Hg increase of

1.2 g/dL

; median reduction % reticulocytes of -

60%

− Hemoglobin increasing throughout the dosing period (maximum increase may not have been reached)

− Reduction in reticulocytes in excess of hemoglobin response, suggests increased oxygen delivery to tissues (kidneys)

• Median reduction in total bilirubin of -

35%

; median reduction of LDH of -

36%

• Persistence of biology (improved deformability,

↑

hemoglobin and

↓

hemolysis) observed after completion of

FT-4202 treatment

(31)

The study will enroll ~344 adult and adolescent patients with SCD

IA, interim analysis; Hb, hemoglobin; HU, hydroxyurea; SCD, sickle cell disease; VOC, vaso-occlusive crises; wk, week

Phase 2/3 study design

DOSE DETERMINATION 60-90 patients, randomized 1:1:1 PLACEBO FT-4202 200 MG ONCE DAILY FT-4202 400 MG ONCE DAILY SCREENING Stratification by: • Age • VOCs (2-3 vs 4-10) in preceding 12 months • Prior/concomitant HU use in preceding 12 months IA1 (12 wk) • Dose selection IA2 (24 wk)

• First primary endpoint (Hb response)

Final Analysis (52 wk)

• Second primary endpoint (annualized VOC)

• Hb response, secondary endpoints

Analyses

52-wk Blinded Treatment Period

EFFICACY CONTINUATION ~274 patients, randomized 1:1 PLACEBO FT-4202 SELECTED DOSE OPEN-LABEL EXTENSION FT-4202 SELECTED DOSE

52 wk

(32)

PKR activation may have a role in other indications, expanding

FT-4202 market impact

Potential to build a Hematology Franchise

β

-Thalassemia and Hemolytic Anemias

Sickle Cell Disease Monotherapy and Combinations

Present

Medium-term

Longer-term

(33)

Forma’s development programs

PKR

Sickle cell

disease

IDH1

AML and Glioma

Partnering

FASN

NASH

partnering

CBP/

p300

Prostate cancer

(34)

Olutasidenib (FT-2102) is a promising mutant-IDH1 inhibitor for

partnering in Glioma and AML

✓

Promising

investigational agent

• Olutasidenib is a selective inhibitor for tumors that express mutant isocitrate dehydrogenase 1

(IDH1m)

• IDH1m produces an onco-metabolite that blocks stem cell differentiation and promotes tumor

progression through epigenetic dysregulation

• IDH1m are found in 70-80% of Glioma and 6-8% of AML patients

• Olutasidenib has shown blood-brain penetration

✓

On-going clinical

programs

• Glioma: Phase 1b

• R/R AML: Phase 2b

✓

Recent data events

• Glioma: 12-month study presented at ASCO 2020, showing disease control in ~50% of patients

(35)

35

Positive topline data for registrational study of olutasidenib

in R/R AML

*While a median duration of CR/ CRh has not been reached, a sensitivity analysis (with a hematopoietic stem cell transplant as the end of a response) indicates the median duration of CR/CRh to be 13.8 months.

▪ 30% CR/3% CRh

▪ 13.8 months median duration by

sensitivity analysis

*

▪ Safety and tolerability data consistent

with Phase 1

1

(36)

Duration of CR/CRh and Overall Response

Overall Response

• Median duration = 11.7 months

CR/CRh Response

• Median Duration (50%) of CR/CRh

not yet reached

o

Estimate of 51

st

_{percentile is}

14.7 months

• In a sensitivity analysis with HSCT

considered as the end of a

response, the median duration was

13.8 months

(37)

Overall Survival by Response Category

Median OS (months)

Safety Population (N=153)

Overall

10.5 (7.7

–

15.6)

Efficacy Evaluable Population (N=123)*

CR/CRh

NR (NR

–

NR)

Non-CR/CRh Responders

15 (5

–

NR)

Non-Responders

4.1 (3.2

–

5.8)

Better response is strongly

associated with longer survival time

CR/CRh estimated 18-month survival

(38)

Preferred Term

All Grades

(N=153)

Grades 3/4

(N=153)

Patients with any TEAEs, n(%)

153 (100)

116 (76)

Nausea

58 (38)

0 Constipation

38 (25)

0 Leukocytosis

38 (25)

14 (9)

Anemia

37 (24)

29 (19)

Pyrexia

35 (23)

0 Febrile Neutropenia

33 (22)

31 (20)

Fatigue

32 (21)

1 (<1)

Thrombocytopenia

28 (18)

24 (16)

Neutropenia

20 (13)

(39)

Forma’s development programs

PKR

Sickle cell

disease

IDH1

AML and Glioma

Partnering

FASN

NASH

partnering

CBP/

p300

Prostate cancer

(40)

• FT-7051 is a novel approach to target androgen receptor (AR) dependent cancers

• FT-7051 inhibits CBP/p300, an essential factor that stabilizes AR and induces

tumor-specific gene expression

• Initial population is mCRPC patients resistant to standard of care, including AR-v7

variant

• Ph1 open for enrollment, safety/tolerability data expected 2H:21, and clinical

activity in 2022

(41)

Significant unmet needs remain in prostate cancer

Prostate cancer deaths

in the US in 2018,

largely attributable to

mCRPC

~30K

Median OS for

AR-v7 mCRPC patients

vs. 27.2 months

10.8 mos.

Leading cause

of cancer

death for men

in the US

(42)

• Expression of splice variants of AR, such as AR-v7, that are always active even in the absence of androgen binding

• Mutation of the AR that enable activation by non-androgen steroids

• Amplification of the AR

• Overexpression of co-activator proteins, including CBP/p300, that enhance AR induced transcriptional activity

• Intra-tumoral synthesis of androgens

• There are no approved therapies for mCRPC with AR resistance variants, including AR-v7

• 5-year survival rate for mCRPC patients progressing on or after first-line chemotherapy is estimated at only 1.6%

• Androgen deprivation therapy (ADT) in combination with the adrenal androgen synthesis inhibitor, abiraterone acetate, or Androgen Receptor (AR) antagonists, such as enzalutamide and apalutamide

Standard of care and unmet clinical need for metastatic

Castration Resistant Prostate Cancer (mCRPC)

Standard of care

Unmet clinical need

(43)

AR-v7 expression predicts unfavorable outcome in mCRPC

AR-v7 prevalence increases with

AR antagonist treatment

1 AR-v7 positive patients have

unfavorable outcome on SoC

2

1. Scher et al. 2016 JAMA Oncol 2. Armstrong et al. 2019 J Clin Oncol

97% 82% 69% 18% 31% Third line Second line 3% First line AR-v7 Other genotype

(44)

FT-7051 is an inhibitor of CBP/p300, an essential co-activator

for AR gene expression

FOXA1 AR CBP p300 AR target genes AR Ac Ac Ac Ac H3K27 H3K27

AR transcriptional activity

FT-7051 has been observed to reduce transcription of AR target genes in AR+ cancers in vitro and in vivo

Chromatin remodeling

Reduced histone acetylation in AR+ prostate cancers in vitro and in vivo

Antitumor activity

• Growth inhibition in prostate cancer cell lines

• Antitumor activity in both enzalutamide-sensitive and resistant prostate cancer PDX mouse models

Inhibition of CBP/p300 is expected to reduce

AR-dependent gene expression and result in clinical

benefit in mCRPC & other AR+ cancers

Protein acetylation AR transcription

Chromatin

remodeling Antitumor activity

Tumor proliferation

(45)

FT-7051 inhibited AR target gene expression and destabilized

AR protein in both androgen-independent & -dependent cells

Androgen-independent cell line

(AR-v7)

Androgen-dependent cell line

(AR wild type)

Source: Forma internal data. Note: FL = full length

a-AR a-b-actin a-AR a-b-actin

Gene

Expression

AR protein

stability

(46)

Cell line Androgen dependence AR alterations FT-7051 IC50 (M) Enzalutamide IC50 (M)

LnCaP Dependent WT, T878A 1.4 1.1

VCaP Dependent WT 0.7 0.4

22Rv1 Independent AR-v7+,

H857Y 0.6 >10

PC3 Independent

AR-negative 8.3 >10 DU145 Independent

AR-negative 8.9 >10

CBP/p300 inhibitors have shown significant anti-tumor activity

in Enzalutamide-resistant prostate cancer lines and PDX models

FT-7051 has been observed to reduce the

proliferation of AR and AR-v7 dependent cell lines

FT-6876 has shown antitumor activity in an

enzalutamide-resistant PDX model

Source: Forma internal data

Note: FT-6876 is research compound; FT-7051 is development candidate

FT-6876 (40 mg/kg) FT-6876 (80 mg/kg) Vehicle control

(47)

With IND cleared, FT-7051 is expected for FPI in early Q1 2021

<1 nM biochemical potency

with >500-fold selectivity

against other bromodomains

Mechanism-based anti-tumor

activity in AR+ cancer models

Predicted efficacious oral

daily doses of 100

–

200 mg

GMP API manufacturing

completed

DP manufacturing completed

Pharmacology and DMPK

Toxicology

Drug substance and drug

_product

No significant in vitro safety

pharmacology findings

GLP toxicology completed

Acceptable

safety/tolerability margins

observed at predicted

human efficacious dose

(48)

CBP/p300 inhibition may have a role in other indications, expanding

FT-7051 market impact

Other AR-dependent cancers

Earlier lines of prostate cancer therapy

AR-v7 and other resistant prostate cancers

Present

Medium-term

Longer-term

(49)

Potential timelines and milestones

Notes: OLE = open label extension

Phase 2: Dose selection

Phase 1 EHA Single dose SCD data ASH MAD1 300mg EHA 12 week OLE ASCO Phase 1 data

FT-4202: SCD

FT-7051: mCRPC

2020 2021

Phase 3: Efficacy continuation IA#1 (12 weeks) Dose Selection 2022 ESMO Phase 1 update FDA Type C IND MAD2 600mg FPI

Phase 1 Single Dose/MAD/OLE

FT-4202: Thalassemia

(TD/NTD)

(50)

Advance FT-4202 and FT-7051 through clinical development for SCD

and mCRPC, respectively

Focused

strategy

Expand clinical development of FT-4202 and FT-7051 into other

indications to maximize commercial opportunity

Continue to build our pipeline in rare hematologic diseases and

cancers with internal research and business development

(51)

Forma’s development programs

PKR

Sickle cell

disease

IDH1

AML and Glioma

Partnering

FASN

NASH

partnering

CBP/

p300

Prostate cancer

(52)

FT-8225, a liver-targeted FASN inhibitor in development for NASH, has a

promising MOA, elucidated safety / PK, and Ph1 ready supply

✓

Promising

investigational agent

FT-8225 is a liver targeted FASN inhibitor. FASN inhibition has been observed to reduce DNL in

the clinic and in preclinical models. Inhibition of DNL reduces steatosis in NASH patients and has

demonstrated activity in NASH pre-clinical disease models.

✓

Animal model-

supported safety

results

~20-fold safety exposure multiples to predicted human efficacious exposure in rat and monkey;

liver-targeted design expected to minimize on-target AEs

✓

Potential combination

use

The FT-8225 CYP-mediated drug-drug interaction risk is low, making it an attractive combination

partner for NASH or NASH-related comorbidities

(53)

FASN inhibition targets a key disease driver of steatosis

De novo lipogenesis

ACC 1/2 Acetyl-CoA FASN Malonyl-CoA Palmitate Lipids

ACCi

FASNi



Malonyl-CoA promotes



TG and



ketone bodies



Malonyl-CoA

Normal EFA metabolism

Carbon from dietary carbohydrates

FASN inhibition does not increase

triglycerides and ketone bodies observed in

ACC 1/2 inhibitors

(54)