Mersana Therapeutics : 2021 Virtual Analyst & Investor Event Presentation

Accelerating ADC

Innovation

…because patients are waiting

Virtual Analyst & Investor Day

January 5, 2021

Legal Disclaimer

This presentation contains "forward-looking" statements within the meaning of federal securities laws. These forward-looking statements are not statements of historical facts and are based on management's beliefs and assumptions and on information currently available to management. Forward-looking statements include information concerning Mersana Therapeutics, Inc.'s (the "Company's") business strategy and the design, progression and timing of its clinical trials, the ability of the single-arm UPLIFT cohort to enable registration, expectations regarding future clinical trial results based on data achieved to date, and the sufficiency of the Company's cash on hand.

Forward-looking statements generally can be identified by terms such as "aims," "anticipates," "believes," "contemplates," "continues," "could," "estimates," "expects," "goal," "intends," "may," "on track," "opportunity," "plans," "poised for," "possible," "potential," "predicts," "projects," "promises to be," "seeks," "should," "target," "will," "would" or similar expressions and the negatives of those terms. Forward-looking statements represent management's beliefs and assumptions only as of the date of this presentation. The Company's operations involve risks and uncertainties, many of which are outside its control, and any one of which, or combination of which, could materially affect its results of operations and whether the forward-looking statements ultimately prove to be correct. Factors that may materially affect the Company's results of operations and whether these forward-looking statements prove to be correct include, among other things, that preclinical testing or early clinical results may not be predictive of the results or success of ongoing or later clinical trials, regulatory changes, particularly with respect to the change in the U.S. presidential administration, the FDA's review of the protocol for our study of the single-arm UPLIFT cohort, and that the development and testing of the Company's product candidates will take longer and/or cost more than planned, as well as those listed in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission ("SEC") on February 28, 2020, the Company's Quarterly Report on Form 10-Q filed with the SEC on May 8, 2020 and subsequent SEC filings. In addition, while we expect that the COVID-19 pandemic might adversely affect the Company's preclinical and clinical development efforts, business operations and financial results, the extent of the impact on the Company's operations and the value of and market for the Company's common stock will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, physical distancing and business closure requirements in the U.S. and in other countries, and the effectiveness of actions taken globally to contain and treat the disease. Except as required by law, the Company assumes no obligation to update these forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

Copies of the Company's Annual Report on Form 10-K and our other SEC filings are available by visiting EDGAR on the SEC website at http://www.sec.gov.

2

Today's Agenda

Topic	Speaker
Opening Remarks	Anna Protopapas, President & CEO
XMT-1536 Pivotal Registration Strategy in	Arvin Yang, MD, PhD, Chief Medical Officer
Ovarian Cancer
	Debra L. Richardson, MD, Associate Professor and
XMT-1536 Phase 1 Ovarian Cancer	Section Chief, Division of Gynecological Oncology at
Expansion Study Data Update	OU Health Stephenson Cancer Center and the Sarah
	Cannon Research Institute
Ovarian Cancer Market Dynamics and	Brian DeSchuytner, SVP Finance & Product Strategy
XMT-1536 Opportunities
XMT-1660B7-H4 ADC Development	Tim Lowinger, PhD, Chief Science & Technology Officer
Candidate
Closing Remarks: 2021 Corporate Goals &	Anna Protopapas, President & CEO
Anticipated Milestones
Q&A

3

2020 Was a Transformative Year for Mersana

XMT-1536

(NaPi2b Dolaflexin)

XMT-1592

(NaPi2b Dolasynthen)

XMT-1660

(B7-H4 DolaLock ADC)

XMT-2056

(1st Immunosynthen ADC)

Corporate

Q1 2020

Q2 2020

Q3 2020

Q4 2020

Q1 2021

SGO:

ASCO:

ESMO and

Today's Strategic

MTD, Proof of

Proof-of-Concept

Fast Track

Update

Activity in NSCLC

in Ovarian Cancer

Designation

Initiated Dose

AACR: Preclinical

Escalation

Data

Declared

Disclosed

Development

Target

Candidate

AACR: Preclinical

Disclosed Dev't

Candidate and

Data

Pipeline

Strengthened

Added

Added

Experienced SVP

Balance Sheet

Experienced CMO

Regulatory

Ended 2020 with Approximately $255 M in Cash,

Funding Current Operating Plan for at Least the Next Two Years

Poised for Significant Value Inflection Points and Continued Momentum in 2021

1. XMT-1536in Ovarian
2. XMT-1536In NSCLC
3. XMT-1592
4. XMT-1660(B7-H4)
5. XMT-2056(Immunosynthen)

Initiate Single-Arm

Registration Strategy

Seek to Achieve Proof-of-Concept

Complete Dose Escalation

IND-Enabling Studies

IND-Enabling Studies

Initiate Lifecycle

Management Studies /

Combinations

Select Lead in NSCLC

IND Submission

Q1 2022

IND Submission

Q1 2022

5

XMT-1536 Has a New Name

upifitamab rilsodotin

or UpRi, for short

6

UpRi (XMT-1536): An Opportunity to Deliver a Potentially Foundational Therapy for Ovarian Cancer

• In a heavily-pretreated ovarian cancer population:
• • Proof of concept, >30% ORR in ovarian cancer with higher NaPi2b expression
  • Activity, including CRs, in patients failing platinum, bevacizumab, and/or PARPi
  • No severe neutropenia, peripheral neuropathy or ocular toxicity
  • Biomarker identification for improved patient outcomes

Earlier Lines of

Therapy

New Combinations

Single-Arm

Registration

Strategy in Platinum

Resistant Disease

INCREASING MARKET POTENTIAL	.

7

UpRi (XMT-1536):First-in-Class Dolaflexin

ADC Targeting NaPi2b

Single-Arm Registration Strategy in

Ovarian Cancer

Arvin Yang, MD, PhD

Chief Medical Officer

UPLIFT Strategy: Key Areas Discussed with FDA

Strategy Informed by End of Phase Meeting and Meeting Minutes

• Population with high unmet medical need
• Performance of current standard of care
• Design of single-arm registration cohort
• Primary and secondary endpoints
• Biomarker validation strategy

9

Appropriate Benchmarks for Current Standard of Care in Platinum-Resistant Ovarian Cancer

With PARPi and bevacizumab increasingly used in earlier lines, the

current standard of care is single agent chemotherapies

			Historical Comparison for
			UPLIFT Population
Study	Demographics	Control Arm	Control Arm Performance
Forward I	1 - 3 Prior	PLD, Topotecan, Weekly	ORR 12%
ESMO 2019	Median 2 Prior	Paclitaxel
	Prior PARPi: 10%
	Prior Bev: 47%
Javelin 200	1 - 3 Prior	PLD	ORR 4%
SGO 2019	Median 2 Prior
Corail	1 - 3 Prior	PLD or Topotecan	ORR 12%
ESMO 2018	Median 2 Prior
	Prior PARPi: 5%
	Prior Bev: 46%

10

UPLIFT: Single-Arm Registration Strategy in Platinum Resistant Ovarian Cancer

Patient Population:

No Pre-Selection for NaPi2b

Inclusion Criteria:

Platinum Resistant Ovarian Cancer

1 - 4 Prior Lines

Exclusion Criteria:

1 - 2 Prior Lines Bev-naïve

Primary Platinum Refractory Disease

Global:	Dose:	N:
US, Europe,
43 mg/m2 q4w	~180 Patients
Australia, Canada

Primary Endpoint:

Confirmed ORR in higher NaPi2b

Key Secondary Endpoint:

Confirmed ORR in overall population

Other Secondary Endpoints:

• Duration of Response
• Safety

11

Significant Time Advantage in Amending with the Single-Arm UPLIFT Cohort

UPLIFT will be operationalized as an amendment as opposed to initiating a new study

Objective

• Determine safety and MTD: 43 mg/m2
• Proof of concept achieved June 2020
• Expansion cohort serves as training set for NaPi2b biomarker
• Demonstrate clinically meaningful outcome
• Validate NaPi2b Biomarker

First in Human to Pivotal Cohort in One Study

Dose Escalation

Cohort

(Enrollment Complete in

March 2020)

Ovarian Cancer Expansion Cohort

(Enrollment August 2019 - Q1 2021)

UPLIFT: Single-Arm Registration Strategy in

Platinum Resistant Ovarian Cancer

(Planning Patient Dosing in Q1 2021)

12

Strategy to Deliver a Robust and Reproducible

Commercial Diagnostic Assay

Ovarian Cancer Expansion Cohort and		UPLIFT: Single-Arm Registration Strategy in
Relevant Doses from Escalation Cohort		Platinum-Resistant Ovarian Cancer

• NaPi2b expression assessed with clinical assay in >80 patients
• "Train" proposed commercial assay
• • Repeat assessment on all samples
  • Ensures same read regardless of lab and pathologist
• Determine cutoff for UPLIFT Pivotal Cohort based on full data set

• Prospectively-definedretrospective analysis validates NaPi2b biomarker cutoff with proposed commercial assay
• Enroll without NaPi2b biomarker selection
• • Evaluate both NaPi2b biomarker higher and overall population
  • Optionality for either companion diagnostic or complementary diagnostic assay

13

UPLIFT Registration Strategy Creates Potential for Speed and Label Differentiation

• Streamlined Execution
• • Leverages expansion cohort enrollment momentum in high unmet need population for single-arm registration path
• Broad Target Population
• • Includes patients with 4 prior lines of therapy, a broader population than historical studies in platinum-resistant ovarian cancer
  • Includes bevacizumab-naïve patients with 3 - 4 prior lines of therapy, accommodating differences in bevacizumab use in early disease
  • No pre-selection accelerates enrollment and provides potential upside opportunity for broad label regardless of NaPi2b expression level
• Assay Validation Process
• • Training and validation method designed to support a commercial assay

Planning to Initiate UPLIFT Patient Dosing in Q1 2021

14

UpRi (XMT-1536):First-in-Class Dolaflexin

ADC Targeting NaPi2b

Phase 1 Ovarian Cancer Expansion Cohort

Data Update

Debra L. Richardson, MD

Associate Professor and Section Chief, Division of

Gynecological Oncology at OU Health Stephenson Cancer

Center and the Sarah Cannon Research Institute

The following information is from an ongoing study and based on December 3, 2020 data cut

Acknowledgements

We thank the patients, their families and caregivers for their contribution to this study

UNTED STATES	UNITED STATES
Allegheny Health Network, Pittsburgh, PA	START Midwest, Grand Rapids, MI
Arizona Oncology Associates, Tucson, AZ	Stephenson Cancer Centre, Oklahoma City, OK
Billings Clinic, Billings, MT	Texas Oncology, Austin, TX
Dana Farber Cancer Institute, Boston, MA	Texas Oncology Fort Worth, Fort Worth, TX
Emory University, Atlanta, GA	Texas Oncology, Tyler, TX
Fox Chase Cancer Center, Philadelphia, PA	University of Alabama at Birmingham, Birmingham, AL
H. Lee Moffitt Cancer Center, Tampa FL	University of Colorado, Aurora, CO
Henry Ford Medical Center, Detroit, MI	University of Florida, Gainesville, FL
Greenville Hospital System University Medical Center, Greenville, SC	University of Miami, Miami, FL
Lahey Clinic, Burlington, MA	University of Pittsburgh Medical Center, Pittsburgh, PA
Levine Cancer Center, Charlotte, NC	University of Tennessee, Knoxville, TN
Mary Crowley Cancer Research Center, Dallas, TX	University of Utah Huntsman Cancer Institute, Salt Lake City, UT
Maryland Oncology and Hematology, Rockville, MD	Virginia Cancer Specialists, Fairfax, VA
Massachusetts General Hospital, Boston, MA	Virginia Commonwealth University Massey Cancer Center, Richmond, VA
Mount Sinai, New York City, NY	Washington University, St. Louis, MO
NEXT Oncology, San Antonio, TX	Willamette Valley Cancer Institute, Eugene, OR
Ohio State University Wexner Medical Center, Hilliard, OH	CANADA
Oncology and Hematology Assoc. of SW VA, Inc., Roanoke, VA	McGill University (Glen-Cedars Cancer Center), Montreal
QUEST Research Institute, Royal Oak, MI	British Columbia Cancer Agency, Vancouver
Rocky Mountain Cancer Centers, LLP, Denver, CO	AUSTRALIA
Sarah Cannon Research Institute, Nashville, TN	Lifehouse Australia as trustee for the Lifehouse Australia Trust, Camperdown
START, San Antonio, TX	Peter MacCallum Center, Melbourne, Victoria	16
	Austin Health, Heidelberg, Victoria

Design for the Ovarian Cancer Cohort of the XMT-1536 (UpRi) Phase 1 Expansion Study

Ovarian Cancer Cohort

• 1-3prior lines in platinum resistant
• 4 prior lines regardless of platinum status
• High grade serous histology
• Archived tumor and fresh biopsy (if medically feasible) for NaPi2b

Patient population: High grade serous ovarian cancer (including fallopian tube and primary peritoneal cancer) progressing after standard treatments

• Measurable disease per RECIST v1.1
• ECOG Performance Status 0 or 1

Dosing: IV every 4 weeks until disease progression or unacceptable toxicity

• 36 mg/m2 cohort initiated in August 2019 and enrollment closed
• 43 mg/m2 cohort initiated in December 2019 and ongoing; current dose evaluated in EXP

Primary Objectives:

• Exclusion: primary platinum-resistant defined as lack of response or disease progression within 3 mos after completing front-line platinum containing therapy

Abbreviations: mos = months; EXP = expansion; RECIST = Response Evaluation Criteria in Solid Tumors; ECOG = Eastern Cooperative Oncology Group; MTD = maximum tolerated dose; ORR = objective response rate; DCR = disease control rate; DOR = duration of response

1Tolcher TW et al. J Clin Oncol 37, 2019 (suppl; abstr 3010)

2Richardson DL et al. Presented at SGO Annual Meeting 2020; LBA8

3 Hamilton E et al. Presented during the 2020European Society of Medical Oncology (ESMO) Virtual Congress

• Evaluate safety and tolerability of MTD
• Assess preliminary efficacy (ORR, DCR)

Secondary Objectives:

• Association of tumor NaPi2b expression and objective tumor response using an immunohistochemistry (IHC) assay with a broad dynamic range to distinguish tumors with higher and lower NaPi2b expression (as previously reported1,2,3)
• Further assessment of preliminary anti-neoplastic activity (DOR)

Assessments:

• Tumor imaging (MRI or CT): baseline and every 2nd cycle; response assessed per RECIST

v1.1	17

Patient Demographics and Disease Characteristics

Data cut off: 03 December 2020

Ovarian Cancer Expansion Patients (N = 72)

Age; years	Median (range)	68 (33, 87)
ECOG Performance Status; n (%)	0	26	(36)
1	46	(64)
Primary Tumor Typea; n (%)	Ovarian	55	(76)
Fallopian Tube	11	(15)
	Primary Peritoneal	6	(8)
Prior Lines of Therapy; n (%)	1-3	47	(65)
4+b	25	(35)
Prior Therapy; n (%)	Bevacizumab	48	(67)
PARP inhibitor	42	(58)
Platinum-free Intervalc; n (%)	0-3 mos	26	(36)
>3-6 mos	39	(54)
	>6 mosd	6	(8)
	Unknowne	1	(1)
BRCA1/2 Mutation; n (%)	Yes	11	(15)
No	52	(72)
	Unknownf	9 (13)
	Determined	54	(75)
NaPi2b H-scoreg; n (%)	Higher	37	(69)
Lower	17	(31)
	Not Yet Determined (ND)	18	(25)

a Includes 1 Endometrioid, 1 Low Grade, 1 Serous / Endometroid, and 1 Carcinosarcoma histology. b Three patients enrolled with 5 prior lines of systemic therapy. c Platinum-free interval defined as the time between the last cycle of most recent platinum-containing regimen and evidence of disease progression; determined from treatment dates and/or clinic notes. d All patients are platinum-sensitive and had received 4 or 5 lines of prior therapy.

e Treatment dates missing/not provided; unable to determine. f BRCA1/2 mutation status not available/not reported. g Higher NaPi2b Expression: as defined in dose escalation as at / above lowest H-score at which response

observed (≥110); Lower NaPi2b Expression: as defined in dose escalation as below the lowest H-score at which response observed (<110); ND = NaPi2b Expression not yet determined or tissue not available

18

XMT-1536 (UpRi) Continues to Have a Consistent Tolerability Profile

• 63 (88%) patients reported at least 1 treatment-related adverse event (TRAE)
• No Grade ≥ 3 (severe) TRAEs of neutropenia, peripheral neuropathy, or ocular toxicity have been reported

TRAEs Reported in ≥20% of Patients with Ovarian Cancer (N = 72)

a

b

c

d

aFatigue includes preferred terms of asthenia and fatigue; bAST increase is transient in nature, recovers to baseline or to Grade 1 prior to the next dose, no instances are associated with elevated bilirubin or cases of Hy's law; cThrombocytopenia	19
includes preferred terms of platelet count decreased and thrombocytopenia. Thrombocytopenia is transient in nature, nadirs at Day 8 and recovers prior to the next dose; dAnaemia includes preferred terms of anaemia and blood loss anaemia;

Safety Summary of XMT-1536 (UpRi) in Patients with Ovarian Cancer (N = 72)

Dose Modifications	Patients,
n (%)
Any dose reduction,
delay, or discontinuation	22 (31%)
due to TRAE
Dose reductions due to	17 (24%)
TRAE
Dose delays due to	8 (11%)
TRAE
Discontinuations due	5 (7%)
to TRAE

SAEs	Patients,	Notes
n (%)
		 SAEs reported in ≥2 (3%) patients
		included:
			5 patients: Gastrointestinal
Any SAEs*	28 (39%)		obstruction (0 related)
		 4 patients each: Abdominal pain (2
			related), pyrexia (4 related), and
			vomiting (3 related)
		 2 patients each: Cerebrovascular
			accident/transient ischemic attack (0
Treatment-			related), pneumonitis (2 related,
Related	11 (15%)		Grade 2 and Grade 5**), pneumonia
SAEs		(0 related), respiratory failure (0
			related), renal impairment (1
			related), fatigue (1 related), and
			atrial fibrillation (0 related)

* Includes both related and unrelated SAEs as assessed by the Investigator
** One grade 5 pneumonitis assessed by the Investigator as related to study drug	20
Abbreviations: SAEs = serious adverse events; TRAE = treatment related adverse event

Case History of G5 Pneumonitis Case and Program Level Review and Modifications

Heavily Pre-Treated87-Year-Old Patient with Recurrent Ovarian Cancer and 4 Prior Lines of Chemotherapy

(carboplatin, paclitaxel, pegylated liposomal doxorubicin, niraparib)

Cycle 2	Initial Presentation: Admitted to Non-Study Hospital
•	Moderate weakness, fatigue, dyspnea, and dizziness
Day 14	•	Treated empirically with diuresis
	•	Discharged to home in stable condition with some improvement

Cycle 2	Re-admitted
• Admitted to cancer hospital with severe fatigue, weakness, and dyspnea
Day 20	• Treated empirically with diuresis and antibiotics with transient improvement
	Diagnosed and Treated for Pneumonitis
Cycle 2	• With worsening symptoms, pulmonary consultation suspected pneumonitis
Day 24	• Started on corticosteroids, complicated by altered mental status and
persistent requirement for high-flow oxygen
	Transitioned to Palliative Care
Cycle 2	• Family concerned respiratory status would not improve
Day 30	• Determined patient would not want more aggressive care
	• Patient was transitioned to comfort care only and died 6 days later

• Safety Review Committee identified a low frequency of pneumonitis cases which were generally low grade and resolved with dose delays, reductions, and/or treatment with steroids
• • 8 additional cases out of 145 treated patients
  • Grade 1/2 n=7, Grade 3 n=1
• Modifications to protocol
• • Enhanced guidance on identification and management of pneumonitis
  • Enhanced Dose delay / reduction guidelines
• No further recommendations received from FDA

21

Continued Robust Activity Observed in Heavily-Pretreated Ovarian Cancer

Best Response in Evaluable Patients with Ovarian Cancer (n = 47)

	All	Higher	Lower	NaPi2b
	NaPi2bO	NaPi2bOO	Not Yet Determined
	(n = 47)
	(n = 31)	(n = 13)	(n = 3)
CR; n(%)	2	(4)	2	(6)	0	0
PR; n(%)	11 (23)	8 (26)	2 (15)	1 (33)
SD; n(%)	19	(40)	13	(42)	5 (38)	1 (33)
PD; n(%)	15	(32)	8 (26)	6 (46)	1 (33)
ORR; n (%)	13	(28)	10	(32)	2 (15)	1 (33)
DCR; n (%)	32	(68)	23	(74)	7 (54)	2 (67)

All Responses are Confirmed

*25 patients were not evaluable for RECIST response: 10 patients discontinued prior to first scans: 1 clinical progression; 1 related SAE (G5 pneumonitis); 3 unrelated SAEs; 5 withdrew consent; 15 patients did not yet have RECIST assessment as of the data cut

1. Higher NaPi2b Expression: defined in dose escalation as at / above lowest H-score at which response observed (≥110) OO Lower NaPi2b Expression: defined in dose escalation as below the lowest H-score at which response observed (<110)

22

Deep Responses Observed in Heavily-Pretreated Ovarian Cancer

Maximum % Change from Baseline in Target Lesions in Patients with Ovarian Cancer (n = 45*)

30/45 (67%) had reductions in target tumor lesions

**

**

• 2 patients not included in waterfall plot as tumor measurement data missing in the database as of data cut; both patients had BOR of PD due to new lesions
• Unconfirmed response, BOR per RECIST v1.1 is SD
• CR of target lesions and non-CR/non-PD of non-target lesions, BOR per RECIST v1.1 is PR

H = Higher NaPi2b Expression; L = Lower NaPi2b Expression; ND = NaPi2b Expression not yet determined or tissue not available

***

23

Responses with XMT-1536 (UpRi) Occur Early and Appear to Deepen Over Time

Change from Baseline in Target Lesions in Patients with Ovarian Cancer (n = 45)

Tumor response observed within 2 cycles in 69% (9 of 13) of Responders

H = Higher NaPi2b Expression; L = Lower NaPi2b Expression; ND = NaPi2b Expression not yet determined or tissue not available

24

Clear Trend to Longer Time on Study with Higher

NaPi2b Expression

Time on XMT-1536 Study in Patients with Ovarian Cancer (n = 72)

Expression	Higher
NaPi2b
Lower

ND

Time on Study (Weeks)

25

Abbreviations: CR = complete response; PR = partial response; H = Higher NaPi2b Expression; L = Lower NaPi2b Expression; ND = NaPi2b Expression not yet determined or tissue not available

Median Duration of Response Estimated to be

~5 Months in Patients with Higher NaPi2b Expression

Durability of Response in Patients with Ovarian Cancer and Higher NaPi2b (n = 10)

Median Duration of Response: ~5 months

• 2 patients with Lower NaPi2b with DOR of 16.1 and 17.1 weeks, respectively

• 1 patient with NaPi2b ND with DOR 16.1 weeks	26

Conclusions: UpRi (XMT-1536) Expansion in Ovarian Cancer

• In this updated analysis of patients with ovarian cancer, UpRi (XMT-1536) continued to be generally well- tolerated with a consistent profile - no severe neutropenia, peripheral neuropathy, or ocular toxicity
• Consistent antitumor activity observed with UpRi (XMT-1536), including patients previously treated with bevacizumab and PARPi
• • Complete response observed in 2 patients with platinum-resistant ovarian cancer
  • Confirmed ORR of 32% and DCR of 74% in higher NaPi2b population
  • Median duration of response ~5 months in higher NaPi2b population
• Trend toward higher response rate as well as deeper and more durable responses in patients with higher NaPi2b expression supports the continued development of NaPi2b diagnostic assay
• These data support the continued development of UpRi (XMT-1536) for the treatment of patients with platinum-resistanthigh-grade serous ovarian cancer who have received 1 to 4 prior lines of systemic therapy

27

UpRi (XMT-1536):First-in-Class Dolaflexin

ADC Targeting NaPi2b

Ovarian Cancer Market Dynamics and

UpRi Opportunities

Brian DeSchuytner

SVP Finance & Product Strategy

Early Use of Bevacizumab and PARP Inhibitors is Changing the Ovarian Cancer Landscape

Prior Lines

Surgery +/- Neoadjuvant Platinum-Based Chemotherapy

• Key approvals moving

0

1-3

1-4

Frontline Therapy

Platinum

Sensitive

Recurrence

Platinum

Resistant

Recurrence

Platinum

Doublet

Platinum

Doublet

PLD,

Topotecan,

Other Chemo

+/- Bev

+/- Bev

Bev + Single

Agent Chemo

(1 - 2 prior)

+/- PARP

Maintenance

+/- PARP

Maintenance

PARP

(if BRCA and

2 - 3 prior)

+/- Bev PARP Maintenance

PARP

(if BRC/HRD 2 - 3 Prior)

targeted therapy into the
frontline
-	PAOLA-1 (Bevacizumab +
	Olaparib maintenance vs
	Bevacizumab)
-	PRIMA (niraparib
	maintenance vs placebo)
-	GOG-218 (Bevacizumab +
	platinum doublet vs platinum
	doublet)

Source: Product Labels, KOL interviews

29

Creating New Unmet Needs and Patient Populations

Prior Lines

0

1-3

1-3

1-4

Frontline Therapy

Platinum

Sensitive

Recurrence

Not

Candidates

for Further

Platinum

Platinum

Resistant

Recurrence

Surgery +/- Neoadjuvant Platinum-Based Chemotherapy

Platinum		+/- Bev		+/- PARP		+/- Bev PARP
Doublet			Maintenance		Maintenance

Platinum				+/- PARP		PARP
	+/- Bev			(if BRCA/HRD
Doublet			Maintenance
				2 - 3 Prior)
PLD,
Topotecan,
Other Chemo
PLD,		Bev + Single		PARP
Topotecan,		Agent Chemo		(if BRCA and
Other Chemo		(1 - 2 prior)		2 - 3 prior)

Unmet Needs

• With emerging evidence of poor outcomes with platinum following relapse after PARPi maintenance, non-platinum combos needed
• Better tolerated, more effective platinum combinations
• Agents with activity following platinum, PARP, and bevacizumab and exceeding 4-12% ORR of single agent chemo

Source: Product Labels, KOL interviews

30

And Opportunities to Evaluate UpRi in Practice Changing Clinical Studies

Prior Lines

Frontline

0 Therapy

Platinum

1-3 Sensitive

Recurrence

Not

Candidates

1-3 for Further Platinum

Surgery +/- Neoadjuvant Platinum-Based Chemotherapy

Platinum		+/- Bev		+/- PARP		+/- Bev PARP
Doublet			Maintenance		Maintenance

Platinum				+/- PARP		PARP
	+/- Bev			(if BRCA/HRD
Doublet			Maintenance
				2 - 3 Prior)

PLD,

Topotecan,

Other Chemo

Platinum Maintenance Combo

Non-PlatinumCombo

1-4	Platinum	PLD,	Bev + Single	PARP
Resistant	Topotecan,	Agent Chemo	(if BRCA and
	Recurrence	Other Chemo	(1 - 2 prior)	2 - 3 prior)

UPLIFT

Source: Product Labels, KOL interviews	31

UpRi Profile May Offer Potential Advantages in Combination

Adverse Events Observed in >30% of Patients Treated with Lifastuzumab Vedotin 2.4 mg/kg + Carboplatin (N=20)

Neutropenia

50%

G3+

Thrombocytopenia

Fatigue

Anemia

Peripheral Neuropathy

55% All

Grade

Hypomagnesemia

Vomiting

Nausea

AST Increased

Grade 3+

Constipation

All Grades

0

20

40

60

80

100

Percentage of Patients

• Roche's lifastuzumab vedotin demonstrated significant overlapping toxicities in combination with platinum
• To date, UpRi has demonstrated activity without severe neutropenia, neuropathy, or ocular toxicity
• Platinum doublets remain the backbone of ovarian cancer therapy in earlier lines, but tolerability limits platinum treatment duration

Moore, K. et al Gynecologic Oncology (2020)

32

UpRi (XMT-1536): An Opportunity to Deliver a Potentially Foundational Therapy for Ovarian Cancer

					Earlier Lines of Therapy
						Treatment and
						Maintenance Options
			New Combinations		under Evaluation
Single-Arm Registration		UPGRADE
	Umbrella Combo Starting
Strategy in Platinum Resistant
	with Platinum
Disease		Additional Combinations
			under Consideration
UPLIFT

INCREASING MARKET POTENTIAL	.

33

XMT-1660:First-in-ClassB7-H4 ADC

Timothy B. Lowinger, PhD

Chief Science & Technology Officer

B7-H4 Expression Well-Suited for a DolaLock ADC

TUMOR CELL

CATABOLIZES ADC

B7-H4

B7-H4

B7-H4

TUMOR

KILLING

IMMUNOGENIC

CELL DEATH (ICD)

• B7-H4is selectively expressed on tumor cells in multiple indications

- Limited expression in normal tissues

B7-H4

• A DolaLock ADC targeting B7-H4 has the potential to exert its effect through multiple mechanisms of action:

Immune	AF-HPA
Diffusion
Response
	Bystander
	Effect
T CELL	ICD
PRIMING

TUMOR

KILLING

DENDRITIC CELL

ACTIVATION BY AF-HPA

Tumor Microenvironment

TUMOR-ASSOCIATED MACROPHAGE CATABOLIZES ADC

BYSTANDER

KILLING

• • Uptake by tumor cells and direct cytotoxicity
  • Released payload can also diffuse to antigen negative tumor cells via the DolaLock controlled bystander effect
  • Tumor cell killing results in immunogenic cell death, and the DolaLock payload activates dendritic cells
  • The DolaLock ADC can provide a combined cytotoxic and immune-basedanti-tumor effect
• B7-H4is also expressed on tumor-associated macrophages which can potentially further contribute to the effect

"The Perfect Storm"

35

Our DolaLock Payload is Both Cytotoxic and Immunostimulatory

AF-HPA induces immunogenic cell death

AF-HPA activates dendritic cells

Calreticulin surface translocation

AF-HPA
(payload)	Dolaflexin ADC

Calreticulin

Control

2.5 hr treatment at1 uM

Calreticulin Calreticulin/Membrane/DNA

Untreated

Dolaflexin ADC 24 hr at 1 uM

ATP release

nM	35
30
ATP	25
Concentration	20
15
	10
	5
	0

LPS (positive control) DMSO (negative control) Dolastatin-10 @ 100 nM AF-HPA @ 100 nM

20 hr treatment of murine BMDC

ICD induction consistent with:	Dendritic cell activation consistent with:	36
Cao et al. 2016; Gardai et al. 2015; Rios-Doriaet al. 2017	Martin et al. 2014; Mueller et al. 2014; Mueller et al. 2015

B7-H4 is Expressed in Multiple Cancer Indications with High Unmet Medical Need

B7H4 mRNA Expression RSEM log 2

Based on mRNA expression data (cBioPortal), high expression in:

• Bile duct carcinoma
• Ovarian
• Uterine
• Breast
• Pancreatic
• Lung squamous
• Bladder
• Etc.

Protein expression data:

• 2-3+ IHC B7-H4 staining/H>50 in >50% of samples in TNBC, uterine, ovarian cancer (Sachdev et al. ASCO, 2019) n= not stated

• B7-H4 Expression (aggregate 1-3+ immunoreactivity) in 77%TNBC, and ~60% HER2+ and HR+ (Leong et al., 2015) n=202

• B7-H4 Expression "High" in ~ 45% of Breast Cancers (Altan et al., 2018) (two cohorts n=561, 444)

• B7-H4 Expression detected in 12.8 and 22.6 % of NSCLC (two cohorts), with higher frequency in SCC (Schalper et al., 2017)

37

Targeting B7-H4 Creates Opportunities to Potentially Address Patients Poorly Served by Checkpoint Inhibitors

PD-L1B7-H4

PD-L1 and B7-H4 expression are essentially mutually exclusive

Case 1

• No co-expression in >95% of breast

cancer and lung cancer samples*

Case 2

Breast Cancer Examples

*Altan et al. 2018 Breast Cancer; Schalper et al. 2016 Clin.Canc.Res.

38

XMT-1660 Selected Candidate Based on Direct Comparison Across Multiple In Vivo Models, including PDX Models

MX-1 TNBC Model

Patient-derived TNBC Model

Solid lines indicate equivalent dose by payload; dashed line = 0.5x dose

Non-binding control ADCs and unconjugated B7-H4 mAb were all inactive; data omitted for clarity XMT-1660

site specific

stochastic

site specific

Dolasynthen DAR 2

Dolaflexin DAR 12

Dolasynthen DAR 6

39

Preclinical Profile of XMT-1660 Supports Advancement

• Pharmacokinetic profile displays long half life (~5 days in NHPs) and dose- dependent exposure
• • Highly stable with very low (<0.1%) free payload detected in circulation
• Well tolerated in NHPs after multiple doses
• Demonstrated therapeutic index based on well-tolerated exposure in NHPs and efficacious exposures in mouse

40

Summary of the Opportunity

• Potential first-in-class opportunity with compelling target biology and unique fit to DolaLock payload
• Clinical candidate was optimized on multiple parameters
• • DAR, site specific bioconjugation, selection of optimal antibody
  • Dolasynthen DAR-6 consistently outperformed stochastic Dolaflexin DAR-12 and site specific Dolasynthen DAR-2 across multiple tumor models
• Expression in areas of high unmet medical need: TNBC, ER+ BC, Endometrial cancer and others
• • Opportunity for accelerated development path in key indications of interest
• Expected to enter the clinic in Q1 2022

41

Corporate Update

Anna Protopapas

President & CEO

UpRi (XMT-1536): Compelling Efficacy and Tolerability Data with Broad Potential in Ovarian Cancer

>30% ORR with CRs in

Ovarian Cancer Patients with Higher NaPi2b Expression

• Majority of patients pre-treated with PARP inhibitors or bevacizumab; 35% with 4 or more prior lines
• • Complete response observed in 2 patients with platinum-resistant ovarian cancer
  • ORR of 32% and DCR of 74% in patients with higher NaPi2b expression
  • Median duration of response: 5 months in higher NaPi2b Population
• Biomarker selects for enhanced outcomes, but responses and stable disease observed in lower NaPi2b population as well

No Severe Neutropenia, Ocular

Toxicity, or Peripheral

Neuropathy

• Most common treatment-related adverse events (TRAEs) were generally Grade 1-2 fatigue, nausea, transient AST elevation without associated changes in bilirubin or cases of Hy's law, transient thrombocytopenia
• Enhanced dose modification and management guidelines for pneumonitis

Single-Arm Registration Strategy

and Expansion Potential in

Combos and Earlier Lines

• UPLIFT includes key differentiators
• • Leverages expansion cohort momentum and no biomarker pre-selection for enrollment speed
  • Broad population up to 4 prior lines, with no prior bevacizumab required for 3 - 4 prior lines
  • Assay validation strategy
• UPGRADE umbrella combination study, with initial platinum cohort, informs strategy in earlier lines

Data as of December 3,2020. Complete ESMO 2020 disclosure available here:https://www.mersana.com/wp-content/uploads/2020/09/Mersana_ESMO-2020_Poster_FINAL.pdf

Complete ASCO 2020 disclosure available here:https://www.mersana.com/wp-content/uploads/2020/05/2020-ASCO_XMT-1536_Poster_FINAL-14May2020.pdf

43

UpRi (XMT-1536): An Opportunity to Deliver a Potentially Foundational Therapy for Ovarian Cancer

					Earlier Lines of Therapy
						Treatment and
						Maintenance Options
			New Combinations		under Evaluation
Single-Arm Registration		UPGRADE
	Umbrella Combo Starting
Strategy in Platinum Resistant
	with Platinum
Disease		Additional Combinations
			under Consideration
UPLIFT

INCREASING MARKET POTENTIAL	.

44

Goals and Anticipated Milestones for 2021

Upifitamab	• Q1 2021: Initiate UPLIFT single-arm registration strategy as amendment
Rilsodotin	• Q3 2021: Initiate UPGRADE combination dose escalation umbrella study
UpRi
(XMT-1536)	• 2H 2021: Report updated interim data from NSCLC expansion cohort
XMT-1592	• 2H 2021: Report dose escalation data
• Q4	2021: Outline further development path
XMT-1660	• Q4	2021: Complete IND-enabling studies to initiate Phase I dose escalation in 2022
XMT-2056	• Q4	2021: Complete IND-enabling studies to initiate Phase I dose escalation in 2022
• Q4	2021: Disclose target
Corporate	• Continue to leverage proprietary platforms to expand pipeline
• Proactively evaluate potential for collaborations that maximize value

45

We are Leveraging our Novel ADC Platforms to Generate Differentiated Product Candidates

						P1 Dose	P1 Proof	P2/Pivotal
ADC Program	Target	Indication	Platform	Discovery	Preclinical	Escalation	of Concept
XMT-1536*	NaPi2b	Ovarian Cancer	Dolaflexin
		NSCLC Adenocarcinoma	Dolaflexin
XMT-1592*	NaPi2b	Ovarian Cancer	Dolasynthen
NSCLC Adenocarcinoma
XMT-1660	B7-H4	Multiple Solid Tumors	Dolasynthen
XMT-2056	Undisclosed	Undisclosed	Immunosynthen
Multiple Programs	Undisclosed	Undisclosed	Immunosynthen
Multiple Programs	Undisclosed	Undisclosed	Dolasynthen or
Dolaflexin
Multiple	Multiple	Undisclosed	Dolaflexin
ASN004	5T4	Undisclosed	Dolaflexin

*NaPi2b antibody used in XMT-1536 and XMT-1592 is in-licensed from Recepta Biopharma. Recepta has rights to commercialize XMT-1536 and XMT-1592 in Brazil

46

We are Leveraging our Novel ADC Platforms to Generate Differentiated Product Candidates

Anticipated Pipeline Progress in 2021

						P1 Dose	P1 Proof	P2/Pivotal
ADC Program	Target	Indication	Platform	Discovery	Preclinical	Escalation	of Concept
XMT-1536*	NaPi2b	Ovarian Cancer	Dolaflexin
		NSCLC Adenocarcinoma	Dolaflexin
XMT-1592*	NaPi2b	Ovarian Cancer	Dolasynthen
NSCLC Adenocarcinoma
XMT-1660	B7-H4	Multiple Solid Tumors	Dolasynthen
XMT-2056	Undisclosed	Undisclosed	Immunosynthen
Multiple Programs	Undisclosed	Undisclosed	Immunosynthen
Multiple Programs	Undisclosed	Undisclosed	Dolasynthen or
Dolaflexin
Multiple	Multiple	Undisclosed	Dolaflexin
ASN004	5T4	Undisclosed	Dolaflexin

*NaPi2b antibody used in XMT-1536 and XMT-1592 is in-licensed from Recepta Biopharma. Recepta has rights to commercialize XMT-1536 and XMT-1592 in Brazil

47

Question & Answer Session