Allogene Therapeutics Reports Positive Phase 1 Data from the ALPHA Trials in Non-Hodgkin’s Lymphoma at the 63rd Annual Meeting of the American Society of Hematology

• ALPHA Trials Demonstrate Potential for AlloCAR T™ Therapy to be a Safe and Durable Alternative to Autologous Cell Therapy in CAR T Naïve Patients
• AlloCAR T Therapy was Associated with Consistent and Manageable Safety with No DLTs or GvHD; Low Rates of Grade 3 ICANs and CRS 
• No Relapses Observed in Large B Cell Lymphoma (LBCL) CAR T Naïve Patients Across Trials Who Achieved a Complete Response (CR) at Six Months
  • Longest Ongoing CRs with ALLO-501 at 18+ Months and ALLO-501A 15+ Months
• Company Plans to Initiate a Phase 2 Pivotal Trial in Relapsed/Refractory LBCL Utilizing Consolidation 1 Dosing with Lower Cyclophosphamide Pending Discussion with FDA
  • Regimen was Well Tolerated with Low Rates of Adverse Events
  • Yielded a 44% CR Rate in LBCL with Ongoing CRs at 9 Months
  • Consolidation Produced an 88% Overall Response Rate and 75% CR Rate in Follicular Lymphoma
• Key Advantage of Allogeneic Delivery Established with >97% of Patients Treated; Median Time from Enrollment to Initiation of Treatment of Five Days in ALPHA and Two Days in ALPHA2 
• Company to Host a Conference Call and Webcast Today at 1:30 p.m. PT/4:30 p.m. ET

SOUTH SAN FRANCISCO, Calif., Dec. 13, 2021 (GLOBE NEWSWIRE) — Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) therapies for cancer, today reported updated data from two Phase 1 clinical trials (ALPHA and ALPHA2) of its lead anti-CD19 AlloCAR T therapy programs (ALLO-501 and ALLO-501A) at the 63^rd American Society of Hematology (ASH) Annual Meeting.

ALLO-501 (ALPHA) data in patients with relapsed/refractory (r/r) large B cell lymphoma (LBCL) or follicular lymphoma (FL) were presented in a poster session by Sattva S. Neelapu, M.D., of The University of Texas MD Anderson Cancer Center. ALLO-501A (ALPHA2) data in patients with r/r LBCL were presented in an oral session by Lazaros J. Lekakis, M.D., of the Sylvester Comprehensive Cancer Center, University of Miami Health System.

“Data from our ALPHA and ALPHA2 trials continue to validate the promise of our AlloCAR T platform to be a safe and durable alternative to approved autologous CAR T therapies,” said Rafael Amado, M.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. “We are excited to leverage the combined learnings from these studies, including the potential advantages of consolidation dosing, as we continue to prepare for a pivotal Phase 2 clinical trial with ALLO-501A for the treatment of relapsed/refractory non-Hodgkin lymphoma.”

“Results from the ALPHA study presented at the 2021 ASH Annual Meeting confirm that ALLO-501 can be safely, effectively and conveniently delivered to LBCL and FL patients, with durable responses observed in both lymphoma subtypes. These data are on par with autologous CAR T therapy and suggest that an off-the-shelf product could be a promising option for patients with relapsed/refractory NHL,” said Dr. Neelapu.

“The ALPHA2 study demonstrates the ability of ALLO-501A to induce deep and durable responses in relapsed/refractory LBCL patients. Consolidation 1 dosing was well tolerated with lower rates of cytopenias and infection while maintaining a similar complete response rate as autologous CAR T therapy. This regimen provides the potential for enhanced efficacy as well as use in an outpatient setting by virtue of its favorable safety profile,” said Dr. Lekakis.

	ALPHA		ALPHA2
Data Cutoff	October 18, 2021
Enrolled	50		29
Evaluable for Safety	49*		28**
Evaluable for Efficacy	40#		25†
% Initiated Treatment	98%		97%
Median Days Enrollment to Treatment Initiation	5		2

^* One patient unable to be treated due to rapidly progressing disease
^** One patient developed COVID-19 before treatment
^# Only CAR T Naïve subjects presented from ALPHA at ASH 2021
^†One patient started LD but became ineligible due to central nervous system disease progression; two treated patients yet to reach tumor assessment at data cutoff

Patients received lymphodepletion (LD) containing fludarabine (30mg/m² x 3 days), cyclophosphamide (Cy) (300mg/m² x 3 days) and ALLO-647 (30, 60 or 90mg) followed by escalating doses of ALLO-501 or ALLO-501A. In consolidation, patients with stable disease or better at Day 28 received a chemotherapy-free lymphodepletion (ALLO-647 only) and AlloCAR T cell infusion (120 x 10⁶ CAR+ T cells). The trials explored two consolidation cohorts. Consolidation 1 used the standard Cy dosing (300mg/m² x 3 days). Consolidation 2 explored a higher Cy dose (500mg/m² x 3 days).

Response Rates Across the ALPHA and ALPHA2 Trials

ALPHA ALLO-501 Response Rates

	Follicular Lymphoma (FL)			Large B Cell Lymphoma (LBCL)
	Single dose (N=18)	Cons (N=8)	All FL (N=26)	Single dose (N=11)	Cons (N=3)	All LBCL (N=14)	All Patients (N=40)
ORR, n (%)	14 (78%)	7 (88%)	21 (81%)	7 (64%)	2 (67%)	9 (64%)	30 (75%)
CR, n (%)	9 (50%)	6 (75%)	15 (58%)	5 (45%)	1 (33%)	6 (43%)	21 (53%)

Consolidation 1 and 2 combined due to limited sample size at the time of the data cutoff

Among the 21 FL patients and 11 LBCL patients who were autologous CAR T naïve, 33% and 36% achieved a complete response at six months. With the exception of one previously disclosed patient who died from unrelated arrhythmia, all LBCL patients who achieved a CR at month six remain in CR with the longest ongoing CR at 18+ months.

ALPHA2 ALLO-501A Response Rates

	DL1/DL2 (N=6)	Cons 1 (N=9)	Cons 2 (N=10)	All Patients (N=25)
ORR, n (%)	2 (33%)	4 (44%)	6 (60%)	12 (48%)
CR, n (%)	2 (33%)	4 (44%)	1 (10%)	7 (28%)
Longest CR (months)	15+	9+	4+	15+

All patients who achieved a CR at month six remain in CR with the longest ongoing CR at 15+ months and longest ongoing CRs in the consolidation cohort at 9+ months.
Combined ALPHA + ALPHA2 Consolidation Response Rates

	Consolidation 1	Consolidation 2	All Patients
	N = 16	N = 14	N = 30
ORR, n (%)	9 (56%)	10 (71%)	19 (63%)
CR, n (%)	7 (44%)	5 (36%)	12 (40%)

Consolidation dosing was associated with meaningful cell expansion after the second dose of AlloCAR T cells. As noted in the ALPHA response rate table, consolidation was associated with a higher ORR (88% vs. 78%) and CR rate (75% vs. 50%) in FL patients versus a single dose of ALLO-501. All seven FL patients who responded to consolidation remain in response with the longest ongoing response at seven months. In the combined Consolidation 1 cohort, four partial responses (PR) converted to CR following the second administration of cells with six of the seven patients in this regimen who achieved CRs remaining in CR.

Safety Across the ALPHA and ALPHA2 Trials

AlloCAR T therapy was associated with consistent and manageable safety with no dose limiting toxicities (DLTs) or graft-vs-host disease (GvHD), and minimal Grade 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), or Grade 3 cytokine release syndrome (CRS). Consolidation 1 presented a superior safety profile across all cohorts.

ALPHA ALLO-501 Safety

	DL1 40M (N=4)				DL2 120M (N=16)				DL3 360M (N=16)				Cons (N=11)				All Patients (N=49)
	All		Gr3+		All		Gr3+		All		Gr3+		All		Gr3+		All		Gr3+
IRR	50	%	0		69	%	6	%	61	%	0		64	%	18	%	63	%	6	%
CRS	0		0		31	%	6	%	33	%	0		27	%	9	%	29	%	4	%
Neurotoxicity	25	%	0		25	%	6	%	22	%	0		36	%	9	%	27	%	4	%
GvHD	0		0		0		0		0		0		0		0		0		0
Infection	75	%	0		63	%	38	%	61	%	17	%	64	%	36	%	63	%	27	%
Neutropenia	100	%	75	%	75	%	75	%	83	%	72	%	82	%	64	%	82	%	71	%
Serious AE	25%				56%				28%				27%				37%

Grade 3+ infection rates were observed at a rate similar to that seen in autologous CAR T trials. There were five treatment-emergent deaths in the absence of disease progression, all of which were previously reported.

ALPHA2 ALLO-501A Safety

	DL1 40M (N=1)			DL2 120M (N=6)				Cons 1 (N=11)				Cons 2 (N=10)				All Patients (N=28)
	All Gr		Gr 3+	All Gr		Gr 3+		All Gr		Gr 3+		All Gr		Gr 3+		All Gr		Gr 3+
IRR	100	%	0	33	%	0		27	%	0		10	%	0		25	%	0
CRS	100	%	0	17	%	0		0		0		10	%	0		11	%	0
Neurotoxicity	100	%	0	33	%	0		9	%	0		20	%	0		21	%	0
GvHD	0		0	0		0		0		0		0		0		0		0
Infection	100	%	0	83	%	17	%	27	%	0		10	%	10	%	36	%	7	%
Neutropenia	0		0	100	%	100	%	36	%	36	%	60	%	60	%	57	%	57	%
Serious AE	0			100%				18%				30%				39%

The safety profile of ALLO-501A was manageable in both the single-dose and both consolidation cohorts. There were no treatment-emergent deaths in the trial. Adverse events of interest in the single-dose cohort were previously reported at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. A chromosomal abnormality is being investigated in a patient in Consolidation 2, which has resulted in a clinical hold on the ALPHA and ALPHA2 trials.   

Pending resolution of the clinical hold and ongoing discussion with the U.S. Food and Drug Administration (FDA), the Company intends to initiate a Phase 2 pivotal trial in r/r LBCL utilizing the Consolidation 1 dosing regimen. In the ALPHA and ALPHA2 trials, this regimen was easy to administer and associated with a favorable safety profile, CR rates on par with autologous CAR T therapies, and supportive biomarker data.

Conference Call and Webcast Details
Allogene will host a live conference call and webcast today, Monday December 13, at 1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time to discuss Allogene data presented at ASH. To access the live conference call by telephone, please dial 1 (866) 940-5062 (U.S.) or 1 (409) 216-0618 (International). The conference ID number for the live call is 1281484. The webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.

About ALLO-501/ALLO-501A (Allogene Sponsored)
ALLO-501 and ALLO-501A are anti-CD19 allogeneic CAR T (AlloCAR T™) products in development for the treatment of relapsed or refractory non-Hodgkin’s lymphoma (NHL). ALLO-501A, a next-generation anti-CD19 AlloCAR T™ intended for Phase 2 development, eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, including NHL patients with recent rituximab exposure. The ALPHA study of ALLO-501 and the ALPHA2 study of ALLO-501A are currently on clinical hold by the FDA.

About Allogene Therapeutics
Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) therapies for cancer. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell therapy candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on Twitter and LinkedIn.

Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the ability to progress the ALPHA2 trial and proceed to the Phase 2 portion of the trial; clinical outcomes, which may materially change as more patient data become available; the ability to resolve the current clinical hold on the Company’s trials; and the potential benefits of AlloCAR T™ therapy. Various factors may cause differences between Allogene’s expectations and actual results as discussed in greater detail in Allogene’s filings with the SEC, including without limitation in its Form 10-Q for the quarter ended September 30, 2021. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

Statements regarding autologous CAR T data are based on review of Kymriah United States product insert (USPI), Schuster S et al NEJM 2019; Yescarta USPI, Locke, AACR 2017; and Breyanzi USPI. Caution should be exercised when interpreting results from separate trials involving separate product candidates. There are differences in the clinical trial design, patient populations, published data, follow-up times and the product candidates themselves, and the results from the clinical trials of autologous products may have no interpretative value on our existing or future results.

AlloCAR T™ is a trademark of Allogene Therapeutics, Inc.

Allogene’s AlloCAR T™ programs utilize Cellectis technologies. ALLO-501 and ALLO-501A are anti-CD19 products being jointly developed under a collaboration agreement between Servier¹ and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S. while Servier retains exclusive rights for all other countries.

Allogene Media/Investor Contact:
Christine Cassiano
Chief Communications Officer
(714) 552-0326
[email protected]

¹ Servier is an independent international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes).

 

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