X4 Pharmaceuticals : Corporate Presentation January 2021

INVESTOR PRESENTATION JANUARY 2021

FORWARD LOOKING STATEMENTS

The statements herein are subject to various risks and uncertainties. These risks and uncertainties include, without limitation, the risk that trials and studies may be delayed and may not have satisfactory outcomes; potential adverse effects arising from the testing or use of mavorixafor or other product candidates; the risk that costs required to develop mavorixafor or other product candidates or to expand our operations will be higher than anticipated; the ongoing direct and indirect effects of the ongoing COVID-19 pandemic on various aspects and stages of X4's clinical development process including the impact to expected site initiation, enrollment and participation in X4's clinical trials; and the risk that the PATH4WARD program and X4's relationship with Invitae will not be successful. Any forward-looking statements herein are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained herein, including, without limitation, the risks and uncertainties described in the section entitled "Risk Factors" in X4's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 5, 2020, and in other filings X4 makes with the SEC from time to time. X4 cautions investors not to place undue reliance on the forward-looking statements herein and undertakes no obligation to update the information contained in this presentation to reflect subsequently occurring events or circumstances.

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Developing treatments designed to have a clear and profound impact for patients suffering from rare diseases, including WHIM syndrome and uncommon cancers

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OVERVIEW: BUILDING A GLOBAL RARE DISEASE COMPANY

• Leading discovery and development of novel therapies targeting diseases resulting from CXCR4 pathway dysfunction
• Novel therapeutics designed to improve immune cell trafficking
• Lead product candidate mavorixafor (X4P-001),first-in-class, oral, small molecule allosteric antagonist of chemokine receptor CXCR4
• Multiple clinical trials underway, including ongoing global registrational
  Phase 3 trial of mavorixafor in WHIM syndrome, a Phase 1b trial in Waldenström's macroglobulinemia and a Phase 1b trial in Severe Congenital Neutropenia
• Potential expansion opportunities across rare disease landscape
• Experienced leadership team in rare disease - includes several former members of Genzyme leadership team
• Headquarters in Boston, MA with R&D facility in Vienna, Austria

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LEADERSHIP:

PROVEN TEAM WITH RARE DISEASE EXPERTISE

M A N A G E M E N T

B O A R D O F DI R E C T OR S

PAULA RAGAN, Ph.D.

CEO

ADAM MOSTAFA

CFO

DIEGO CADAVID, M.D.

CMO

ART TAVERAS, Ph.D.

CSO

DEREK MEISNER, J.D.

General Counsel

MARY DIBIASE, Ph.D.

SVP of Technical Operations & Quality

CARRIE MELVIN

SVP of Development Operations

SHARIQ ALI, Ph.D.

VP of Medical Affairs

MICHELE RHEE, M.P.H., M.B.A.

VP of Patient Advocacy

MICHAEL WYZGA, Chairman

BILL ALISKI

GARY BRIDGER, Ph.D.

DAVID MCGIRR, MBA

PAULA RAGAN, Ph.D.

MURRAY STEWART, M.D.

RENE RUSSO, PharmD, BCPS

ALISON LAWTON

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MAVORIXAFOR: TARGETED TREATMENT FOR DISEASES DRIVEN BY IMMUNE-CELL TRAFFICKING DEFICITS

ME C H A N I S M O F A C T I ON

PHASE 3:

WHIM Syndrome

PHASE 1B:

Waldenström's

Macroglobulinemia

L E A D I N D I C A T I ON S

Validated by blocking "Gain-of-Function" CXCR4 genetic mutations

L A B E L E X P A N S I ON O P P O RT U NI T IES

PHASE 1B:
Severe Congenital	Immune-suppression
Neutropenia
corrected by
PHASE 2A:	blocking CXCR4 Signaling
Renal Cell Carcinoma*
	P I P E L I NE
PRECLINICAL	Established linkages to
PROGRAMS:
immune-system
Additional primary
genetics/pathways
immuno-deficiencies

* Exploring potential strategic partnership(s) for future development and potential commercialization for mavorixafor for ccRCC and other potential immuno-oncology indications

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OVERVIEW: MAVORIXAFOR

First-in-class CXCR4 antagonist

• Small molecule with high potency and selectivity
• Terminal half-life of 22 hours
• Formulated as a once-daily oral capsule

Clinical trial experience in nearly 200 patients

Alignment on global Phase 3 trial design and regulatory path for WHIM

• Breakthrough Therapy Designation in U.S.
• Fast Track Designation in U.S.
• Rare Pediatric Disease Designation in U.S.
• Orphan Drug Status in U.S. and Europe

Critical U.S. composition of matter patents expected to provide protection through 2038

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PRODUCT PIPELINE

CANDIDATE	INDICATION	PRECLINICAL	PHASE 1	PHASE 2	PHASE 3
	Warts, Hypogammaglobulinemia, Infections
				P H A S E	3
	and Myelokathexis (WHIM) syndrome1
Mavorixafor	Waldenström's Macroglobulinemia (WM)
P H A S E 1 B
(X4P-001)
	Severe Congenital Neutropenia (SCN)
	P H A S E 1 B
	Clear cell renal cell carcinoma2,3 (ccRCC)			P H A S E 2 A
	(Combination with Inlyta®)
X4P-002	Glioblastoma multiforme (GBM)
X4P-003	Primary immuno-deficiencies (PID)

• Phase 2 open label extension trial for WHIM ongoing and Phase 3 trial initiated

• Two oncology trials have concluded: Phase 1b biomarker in melanoma and Phase 1b in ccRCC. Positive data from ccRCC Phase 2a trial reported at ESMO 2019

• Intend to enter into a strategic partnership for future development and potential commercialization for mavorixafor for ccRCC and other potential solid tumor immuno-oncology indications

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LEAD INDICATIONS: CXCR4 MUTATIONS AS A DRIVER OF DISEASE

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ABOUT WHIM SYNDROME

• Warts - can lead to HPV-related cancers

• Hypogammaglobulinemia

• Infections

Immunodeficiency caused by gain-of-function mutations in the CXCR4 receptor that lead to excessive "on-signaling," compromising immune cell trafficking and the ability to mount a healthy immune response

• maturemarrowneutrophils in the boneMyelokathexis - retention of

>3,500	1			mutations
		11	known pathogenic
estimated U.S. WHIM	Approved	targeted therapies
0
population	Symptomatic Rx; antibiotics, G-CSF,
		immunoglobulins	Genetic test to diagnose

1. Qessential Market Research 2019; IPM.ai AI research study, 2020

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UNMET NEEDS IN WHIM

WHIM

SYNDROME

	Infections
Critically low white	Bacterial
blood cell counts, due
to myelokathexis, results
in immunosuppression

HPV infections

disfiguring recalcitrant warts; HPV-associated cancers

Severe bacterial infections in multiple organ systems

Bronchiectasis (lung), hearing loss (ear), cellulitis (skin)

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PHASE 2 TRIAL INFORMS PHASE 3 TRIAL

P H A S E 2 T R I A L D E S I G N

INCLUSION

• Neutrophil count: ANC ≤400/μL and/or
• Lymphocyte count: ALC ≤650/μL or both

DOSE ESCALATION + OPEN-LABEL EXPANSION

• Dose Escalation: 50 to 400mg oral capsule once daily (QD), N = 8 patients
• Open-LabelExpansion: If completed >24 weeks of dose escalation (N=5)

ENDPOINTS & ASSESSMENTS

• Safety, infections, warts, pharmacokinetics (PK) / pharmacodynamics (PD) to support dose-selection
• Open label extension examined infection rates, warts, long-term safety
• Primary Endpoint for Phase 3: 24-hr Time (hrs.) Above Threshold of Absolute Neutrophils Count (TATANC)

I L L U S T R A T I V E T R I A L E N D P O I N T E X A M P L E

	1250
					TREATMENT GOAL
Cells/uL-
1000			0 HRS	< TAT	ANC	<	24 HRS
				BASELINE			MAXIMUM
(ANC)	750
COUNT		"TATANC"		Threshold (500 cells/ul)
NEUTROPHIL	500
250
		Inclusion Criteria: WHIM patient ANC ≤400/μL; TAT baseline ~ 0
	0
	0	6	12		18		24

HOURS

OBJECTIVE: INCREASE DAILY NEUTROPHIL COUNTS (ANC) ABOVE THRESHOLD AS MEASURED OVER 24 HOURS: TIME ABOVE THRESHOLD (TAT)

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WHIM PHASE 2: OPEN-LABEL EXTENSION

SUCCESSFULLY ADDRESSED ALL 3 UNMET NEEDS

• Mavorixafor 400 mg orally once daily was well tolerated for >2 years without attributable serious AEs
• Durable, dose-dependent increases of WBC, ANC, and ALC counts
• TATANC is an objective and consistent biomarker of clinical response to CXCR4 antagonist therapy
• • Primary endpoint in ongoing Phase 3 global clinical trial

Demonstrated increase in TATANC at least	Increased total white blood cell counts
4.5-fold versus lower doses

At 300/400 QD Doses: Mean TATANC was 12.6 hours

400 mg QD: largest WBC increase vs. baseline

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Data from X4 poster presentation at 2020 EHA

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WHIM PHASE 2: OPEN-LABEL EXTENSION SUCCESSFULLY ADDRESSED ALL 3 UNMET NEEDS

• Durable, dose-dependent increases of WBC, ANC, and ALC counts led to clinical benefits

INFECTION RATES

• Infection rates decreased from 4.63 in the 12 months prior to the trial, to 2.14 (a 54% reduction) at 400 mg
• Deepening reductions in infection rates with time

WART BURDEN

• Average 75% reduction in the number of warts
• Baseline vs. 18 months, following 14 months on 400 mg mavorixafor

Two key secondary

endpoints in

ongoing pivotal

Phase 3 trial

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Data from X4 poster presentation at 2020 EHA

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ESTABLISH

TAT

BASELINE

GLOBAL REGISTRATIONAL PHASE 3 TRIAL IN WHIM SYNDROME

P R I M A R Y E N D P O I N T A S S E S S E D

3 mos.	6 mos.	9 mos.	12 mos.

		MAVORIXAFOR (N=9)1
					ROLLOVER
1 : 1					TO
RANDOMIZATION				OPEN-LABEL
					TRIAL

PLACEBO (N=9)1

• Primary Endpoint: Biomarker of neutrophil count time above threshold (TAT) where the threshold is defined as 500 cells/uL; average of four assessment timepoints
• Secondary Endpoints: Infection rates and wart burden assessments
• Dosing: 400mg QD in patients 12 years of age or older
• Enrollment: Plan to enroll 18 to 28 subjects and activate approximately 20 to 25 sites globally
• Phase 3 Top-line Data: expected in 2022

1. Allowed to enroll up to 14 patients on drug and 14 patients on placebo

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OVERVIEW: WALDENSTRÖM'S MACROGLOBULINEMIA (WM)

• Rare blood cancer: form of Non-Hodgkin's Lymphoma
• Manifestations1
• • Hyperviscosity syndrome
  • Cryoglobulinemia/skin lesions
  • Cold agglutinemia
  • IgM neuropathy
  • Reduced iron/anemia
  • Enlarged lymph nodes/spleen
  • Bing Neal Syndrome (CNS infiltration)
• ~8-yearsurvival rate post-diagnosis2,3

• https://www.iwmf.com/about-wm/signs-and-symptoms

• Sekhar J, et.al.. Waldenström macroglobulinemia: a Surveillance, Epidemiology, and End Results database review from 1988 to 2005. Leuk Lymphoma 2012;53(8):1625-1626;
  3https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=33226

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INCREASE IN CANCEROUS B-CELLS AND SERUM IGM IN WM: DRIVEN BY GENETIC MUTATIONS IN MYD88 & CXCR4

B-Cell

TLR4	IL1R	CXCR4	Normal B-Cells
Produce:

Normal Bone

Marrow Serum IgM: ~150 mg/dL

MYD88 MYD88

BTK

Cancerous

WM B-cells

Produce:

Serum IgM:

Waldenstrom's 1000 to >5000 mg/dL

>90% Have Mutations	30-40% Have	Increased Survival, Proliferation,
WHIM-like Mutations
in MYD881	Migration of Cancer Cells
in CXCR42

1. Treon et al. 2012. New England Journal of Medicine, 367, 826-833; 2. Hunter et al. 2014. Blood, 123, 1637-1646.

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IgM LEVELS: MAJOR METRIC IN "RESPONSE RATES" FOR REGISTRATION TRIALS

"Response" Definitions in WM - Two Components

1. Decreasing Serum IgM Levels (Normalized To Pre-RxBaseline)

1	0.75	0.5		0.1
Progressive
Disease (PD)	Stable			Major Response (MR)
			Disease (SD)	Minor
				Response
						Partial
						Response (PR)
								Very Good
	higherordecreaseNo baselinethanlevel							Partial
							Response
								(VGPR)
			Up to 25%	25-50%		50%-90%		>90%
			Decrease	Decrease		Decrease
					Decr.

Complete

Response (CR)

Normal IgM

Current Treatment Options - Response Rates1

• ~No CRs
• 13%-27%VGPR rates
• 71-84%MR rates

WM Patients with CXCR4 mutations - Response Rates with Ibrutinib2,3

• ~No CRs
• ~10% VGPR rates
• ~60% MR rates
• ~4-foldlikelihood ibrutinib discontinuation

Normal/

Healthy

2. Decreasing Clinical Symptoms & Extramedulary Disease (If Present)

1. Castillo and Treon, Leukemia, 2019. 2. Treon et al, EHA 2018; 3. Treon et al, EHA 2018

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CXCR4-MUTANT WM PATIENTS:

EARLY IGM KINETICS & EARLY RESPONSE RATES

New Therapies Should Deliver

• Faster Time to Major Response
• Increased Major Response Rates within the first 24 weeks and beyond

PREVIOUSLY	FRONT LINE
TREATED - Rx	Rx w/
w/ Ibrutinib3,5	Ibrutinib4
Time to Major	6.0	7.3
Response1
(months)
Major Response	28.6%	28.6%
Rate2(%) at 12
weeks
Major Response	38.1%	28.6%
(%) at 24 weeks

Front Line Rx with Ibrutinib

IgM vs. Time4

		1.25
	(normalized to pre-treatment baseline)	1
Serum IgM Levels	0.75
0.5
0.25
0
0	2	4	6	8	10	12
	Months on Treatment

1. Time (months) Major Response is time (months) until serum IgM levels drop by 50% or more.
2. Major Response defined as Partial Response (PR) or better as best response on treatment.
3. Treon et al, NEJM, 2015; 372:1430-40. (Rx -second thru 4th line)
4. Treon et al, JCO, 2018; 36:2755-2761. (Rx -first line)
5. Treon et al, EHA abstract PS1185, 2018.

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WM PHASE 1B TRIAL UNDERWAY:

FOCUS ON DOUBLE-MUTANT REFRACTORY/RECURRENT

Inclusion: Patients with MYD88 + CXCR4 mutations who are naïve to ibrutinib

Design: Multi-national Phase 1b trial of mavorixafor in combination with ibrutinib (n=12 to 18)

• Intrapatient dose-escalation: cycles of 200 mg to 600 mg with extension on highest tolerated dose for additional 3 months
• 3 cohorts supporting dose selection of mavorixafor:
• • Cohort A: 6 patients dosed up to 400 mg*
  • Cohort B: additional 6 patients dosed up to 600 mg
  • Cohort C (expansion): potential for additional 6 patients dosed up to 600 mg
• Endpoints: safety, PK/PD, and assessments of serum IgM levels and other blood parameters

Timing: Initial data in 1H 2021

• Strategic collaboration with Leukemia & Lymphoma Society (LLS)
• Selected for LLS' Therapy Acceleration Program

* Cohort A are eligible to dose escalate to 600 mg after Cohort B completes first 600 mg cycle.

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LABEL EXPANSION OPPORTUNITIES

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OVERVIEW: SEVERE CONGENITAL NEUTROPENIA (SCN)

• Rare blood disorder
• Characterized by abnormally low levels
  of certain white blood cells (neutrophils <1,500 cell/ul)1
• • From birth, fevers, severe bacterial infections
    (at times life-threatening), pneumonias, oral ulcers, premature tooth loss
  • Treatment options: antibiotics and G-CSF
• Prevalence estimated 2,000-3,000 patients (US & EU)2
• Genetic drivers:
• • May be inherited as either an autosomal dominant or an autosomal recessive genetic trait
  • Many cases of SCN are the result of

spontaneous, random mutations	Oral ulcers

1. https://rarediseases.org/rare-diseases/severe-chronic-neutropenia/ 2. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=42738

Chronic G-CSF

Injections

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PHASE 1B SCN TRIAL UNDERWAY:

FOCUS ON NEUTROPHIL RESPONDERS

14 - DAY EXPLORATORY TRIAL ASSESSING FOR RESPONDERS TO MAVORIXAFOR

PATIENT PROFILE		DAY 0		DAY 1, DOSE 1		DAY 14, DOSE 14

Severe Chronic				If Day 1 ANC >25%
Idiopathic Neutropenia
	Baseline		over baseline within		Final
population and
	ANC1		8 hours, continue		ANC1
exploratory
			daily mavorixafor
sub-populations

Inclusion: Up to 45 patients total (30 SCN, 15 exploratory sub-populations)

Endpoints: Safety and tolerability, percentage of patients with ANC >50% baseline

Goal: Achieve proof of concept to support FDA interactions regarding proposed registrational trial

• Measured over first 8-hours of baseline assessment or dose

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CLINICAL EPIDEMIOLOGY SUGGESTS SIGNIFICANT MARKET OPPORTUNITY

De-risked MOA targeting the CXCR4 pathway positions X4 to treat

>10,000 total patients with rare diseases

>3,5001

D I A G N O S E D & U N D I A G N O S E D

W HIM

S YNDROME

4,000 - 5,0002	2,000 - 3,000	3
WALDENSTRÖM'S	S E V E RE CONGE NITAL
MA CROGLOBULINEMIA	NE UT ROPENIA
(W M)	(S CN)

• Strong Phase 2 results de-risk ongoing Phase 3
• Favorable Breakthrough Therapy Designation

•	Near-term	Neutropenia
	inflection point	expansion
•	Large, well defined	opportunities
	market opportunity

• Qessential Market Research 2019 and IPM.ai, 2020 - number of potential undiagnosed represents estimates for US only from AI study
  2 Represents CXCR4-mutant patients; 30% to 40% of total WM estimate of 13,000 patients in the U.S. and EU; 3 Estimated U.S. and EUhttps://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=42738

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EFFORTS TO MAXIMIZE MAVORIXAFOR POTENTIAL

Sponsored Genetic Testing

MSL Deployment to engage

concentrated, targeted physician population

Disease Education on WHIM and Waldenstrom's

Ongoing Collaboration with key Patient Advocacy

Groups

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COMPLETED AND ANTICIPATED MILESTONE ACHIEVEMENTS

TARGET DATE

2019

2019

2019

1H 2020 Mid-2020 1H 2021 2021 2022

MILESTONES

Phase 1b trial in SCN: initiated

Breakthrough Therapy Designation granted by FDA for treatment of adult WHIM patients Phase 1b trial in Waldenström's: initiated

WHIM prevalence update: raised guidance

Positive WHIM Phase 2 open-label extension data presented at EHA

Phase 1b trial in Waldenström's: initial data readout

Phase 1b trial in SCN: initial results

Phase 3 trial in WHIM: topline results

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SELECTED FINANCIAL INFORMATION

$90.7M1

A N A L Y S T C O V E RA G E

Cash Expected to Fund Operations into 2022

Share and Warrant Information:

• 20 . 2M shares outstanding

( 1 6 . 3 M c o m m o n s h a r e s a n d 3 . 9 M p r e - f u n d e d w a r r a n t s )

• 5 . 4M class B w arrants

( e x p i r y j u s t p o s t W H I M P 3 d a t a )

• 3 . 9M class A w arrants

( 2 0 2 4 e x p i r y)

BIOTECH - FOCUSED INSTITUTIONAL SHAREHOLDER BASE

1 A s o f S e p t e m b e r 3 0 , 2 0 2 0 , a s r e p o r t e d i n t h e C o m p a n y ' s f o r m 1 0 - Q f i l e d w i t h t h e S E C o n N o v e m b e r 5 , 2 0 2 0 .

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INVESTOR PRESENTATION JANUARY 2021

APPENDIX

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IMMUNO-ONCOLOGY STRATEGY:

PARTNERSHIPS TO CAPTURE GLOBAL VALUE

COMPLETED TRIALS DEMONSTRATE SINGLE AGENT ACTIVITY & PROOF OF MECHANISM

POSITIVE DATA FROM PHASE 2A ccRCC TRIAL: MAVORIXAFOR + AXITINIB

PRESENTED AT ESMO 2019

• Phase 2a Trial:
• • Inclusion: 65 patients, multi-national, fully enrolled
  • Assessment: 4.8 months mPFS with axitinib in patients with immediate prior TKI
  • Objective: >50% improvement in medium PFS
• Conclusions:
• • Combination therapy with 400mg QD mavorixafor + 5mg BID axitinib observed to be generally well-tolerated with a manageable safety profile
  • • Overall mPFS across clinically evaluable patients (n=62): 7.4 months
  • Demonstrated encouraging mPFS in this heavily pretreated advanced RCC patient population
  • • mPFS with immediate prior IO therapy (n=18): 11.6 months
    • mPFS with immediate prior TKI therapy (n=34): 7.4 months
    • 8 patients remain on study > 17 months
  • Results suggest that mavorixafor may enhance clinical responses to axitinib and other TKIs that target tumor angiogenesis, as well as immunotherapy agents, such as CPIs
• Strategy: Identify strategic collaborators to advance in IO
• • Entered into partnership with Abbisko Therapeutics to develop mavorixafor in solid tumor oncology indications. We have retained all ex-China rights and can leverage data generated by Abbisko

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IGM LEVELS: MAJOR METRIC IN "RESPONSE RATES" FOR REGISTRATION TRIALS

Based on Best Responses: typically 6 months or later in trials

Response		Response
Category		Requirements
Complete	• Absence of serum monoclonal IgM protein by immunofixation
• Normal serum IgM level
Response
• Complete resolution of extramedullary disease
(CR)
• Morphologically normal bone marrow aspirate trephine biopsy
Very Good	•	Monoclonal IgM protein is detectable >/= 90% reduction in serum
Partial		IgM level from baseline
Response	•	Complete resolution of extramedullary disease
(VGPR)	•	No new signs or symptoms of active disease
	• Monoclonal IgM protein is detectable >/= 50% but <90%
Partial		reduction in serum IgM level from baseline
Response (PR)	•	Reduction in extramedullary disease
	• No new signs or symptoms of active disease
Minimal	•	Monoclonal IgM protein is detectable >/= 25% but <50%
Response		reduction in serum IgM level from baseline
(MR)	•	No new signs or symptoms of active disease
	• Monoclonal IgM protein is detectable <25% reduction and <25%
Stable Disease		increase in serum IgM level from baseline
(SD)	•	No progression is extramedullary disease
	• No new signs or symptoms of active disease
Progressive	• >/= 25% increase in serum IgM level from lowest nadir (requires
	confirmation)*
Disease (PD)
•	And/or progression in clinical features attributable the disease

Current Treatment Options - Response Rates1

• ~No Complete Responses
• 13%-27%VGPR Rates (IgM decrease of >90%)
• 71-84%Major Response Rates (MRR) (IgM decrease of >50%)

WM Patients with CXCR4 mutations - Response Rates w/Ibrutinib2,3

• ~No Complete Responses
• ~10% VGPR & ~60% MRR
• Progression Free Survival (mPFS) for CXCR4WHIM less than half that for wild-type
• ~4-foldlikelihood ibrutinib discontinuation

*An absolute increase of >5 g/L (0.5 g/dL) is required when the increase of IgM component is the only applicable criterion

1. Castillo and Treon, Leukemia, 2019. 2. Treon et al, EHA 2018; 3. Treon et al, EHA 2018

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