Immutep : announces publication of SITC 2021 posters

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ASX/Media Release

Immutep Publishes AIPAC, TACTI-002 and TACTI-003 Trial Posters at SITC

with Positive New Data for LAG-3 Therapy, Eftilagimod Alpha

• AIPAC poster presentation includes new data and graphs showing:
• • Very encouraging Overall Survival (OS) data from the abstract published on 9 November 2021, including statistically significant benefit in 3 patient subgroups representing a majority of patients
  • A statistically significant Quality of Life preservation in first 6 months in the eftilagimod alpha ("efti") group in total population
  • The statistically significant increase in peripheral CD8 T cells in patients in the efti group of the total population1 and the statistically significant correlation of this increase with improved OS
• TACTI-002 poster presentation of more mature interim data from 2nd line head and neck squamous cell carcinoma (HNSCC) patients (Part C):
• • Encouraging Overall Response Rate (ORR), with 29.7% (11/37) of 2nd line HNSCC patients responding to the combination therapy of efti and pembrolizumab
  • Favourable duration and depth of responses, with 5 Complete Responses and a minimum duration of response extended to > 9 months across all responding patients
  • Responses continue to be seen in PD-L1 low and high expressors
  • Further data from TACTI-002 is expected to be reported in H1 calendar year 2022
• TACTI-003 is a Phase IIb multicentre, open label, randomised and controlled, trial enrolling approximately 154 patients with 1st line HNSCC

SYDNEY, AUSTRALIA - 15 November 2021 -Immutep Limited(ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel LAG-3 related immunotherapy treatments for cancer and autoimmune disease, announces new data has been published in poster presentations at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2021 which took place from 10-14 November 2021 in the US. The new data relates to the Company's Phase IIb AIPAC trial and Part C of its Phase II TACTI-002 study (also designated KEYNOTE-798). In addition, a poster presentation of the trial design of the Company's new randomised Phase IIb study in 1st line HNSCC was also presented at SITC.

All three poster presentations relate to Immutep's lead candidate efti and are available on the Company's website: https://www.immutep.com/investors-media/presentations.html.New data which is shown in addition to the data from the abstracts released on 9 November 2021 is summarised below.

Immutep will present data from the posters in a global webcast for investors on Wednesday, 17 November 2021 at 8.00 am AEDT / Tuesday, 16 November 2021 at 4.00 pm EST. Details are below.

PHASE IIB AIPAC POSTER PRESENTATION

In addition to the final OS data announced on 10 November 2021, Immutep reports new Quality of Life (QoL) data from AIPAC. QoL is a secondary endpoint of the study. In the total trial population, a statistically significant QoL preservation was observed in the first 6 months in the efti group of patients who were treated with efti in combination with paclitaxel. This compares favourably to the comparator group (paclitaxel and placebo) where a significant deterioration in these measures were reported at 6 months

1 Immune monitoring was conducted on a selection of patients from the total population: N=36/31 comparator group/efti group.

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(see Figure 1). QoL is generally very important for patient compliance and forms part of reimbursement discussions after any potential marketing approval.

Figure 1. Quality of Life at 3 and 6 months of treatment (Global Health Status / QoL QLQC30-B23)2

As previously announced, the AIPAC trial demonstrates a statistically significant and clinically meaningful OS benefit in now three prespecified (prior to unblinding) patient subgroups. A majority of patients fall into at least one of the patient subgroups and therefore derive a statistically significant benefit (Table 1).

• Patients under the age of 65 years (representing 66.7% of patients in the efti group) reported a median OS of 22.3 months compared to 14.8 months in the comparator group, indicating an absolute survival benefit of +7.5 months (HR = 0.66; p = 0.017) favoring the efti group (see Figure 2).
• Patients with a low monocyte count (< 0.25/nl) at the commencement of the study (representing 21.9% of patients in the efti group) reported a median OS of 32.5 months compared to 12.9 months in the comparator group, indicating an absolute survival benefit of +19.6 months (HR = 0.44; p = 0.008) favoring the efti group.
• Patients with a more proliferating tumor cell type expressing more neo-antigens (i.e. leading to more immunogenicity), characterised as luminal B (representing 48.8% of patients in the efti group) reported a median OS of 16.8 months compared to 12.6 months in the comparator group, indicating an absolute survival benefit of +4.2 months (HR = 0.67; p = 0.049) favoring the efti group.

Figure 2. Kaplan-Meier curve for OS in patients < 65 years of age

2 * Differences are statistically significant.

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Table 1 - Overall Survival in key patient subgroups at final analysis at 72.5% of events in the overall population

	Group			% of patients in		Efti group /		Median OS		Absolute OS benefit
			efti group		Comparator group		(months)		from efti
						Efti + paclitaxel	20.4		+2.9 months
	Total Population			100%						HR = 0.88
				Placebo + paclitaxel	17.5
							p = 0.197
						Efti + paclitaxel	22.3		+7.5 months
	< 65 years old		66.7%						HR = 0.66
			Placebo + paclitaxel	14.8
							p = 0.017
	Low monocytes				Efti + paclitaxel	32.5		+19.6 months
		21.9%						HR = 0.44
	< 0.25/nl
			Placebo + paclitaxel	12.9
					p = 0.008
						Efti + paclitaxel	16.8		+4.2 months
	Luminal B	48.8%						HR = 0.67
		Placebo + paclitaxel	12.6
							p = 0.049

Pleasingly, these results have improved since interim data were reported at the San Antonio Breast Cancer Symposium (SABCS) in December 2020. A comparison is provided in Table 2.

Table 2 - Comparison of interim Overall Survival data and final Overall Survival data

		Interim data		Final data		Median OS
	Group	(SABCS 20)		(SITC 21)		improvement
				[months]
		+2.7 months		+2.9 months
	Total Population	HR = 0.83		HR = 0.88		+0.2
		p = 0.14		p = 0.197
		+7.1 months		+7.5 months
	< 65 years old	HR = 0.62		HR = 0.66	+0.4
		p = 0.012		p = 0.017
	Low monocytes	+9.4 months		+19.6 months
	HR = 0.47		HR = 0.44		+10.2
	< 0.25/nl
	p = 0.02		p = 0.008
		+3.8 months		+4.2 months
	Luminal B	HR = 0.69		HR = 0.67	+0.4
		p = 0.077		p = 0.049

In addition, as briefly reported on 10 November 2021, immune monitoring studies showed an increase in peripheral CD8 T cells in patients from the efti group of the total population (N=36/31 comparator group/efti group).1 This increase is statistically significant and is also significantly correlated with improved OS, demonstrating strong proof-of-concept. New data and graphs are provided below (see Figures 3 & 4).

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Figure 3. Mean ± SEM of absolute count of CD8	Figure 4. Correlation between cytotoxic CD8 T
T cells* prior next dosing	cells and OS
months		900	Placebo	Rho= -0.2; p= 0.5
6 )	700	30 mg efti	Rho= 0.6; p= 0.007
at blood	500
countcell	(10
	of/L
	6
		300
T
CD8		100
		10	20	30	40	50
			Overall survival (months )

Immutep CEO, Marc Voigt commented: "The combination of the OS data in the prespecified subgroups, immune monitoring data and Quality of Life data, which were all statistically significant, give us confidence as we move forward with the development of efti in various late-stage settings. The results here are particularly noteworthy because Her2-HR+ metastatic breast cancer is not a particularly immunogenic tumour and so does not always respond to treatment with modern immunotherapies such as anti-PD-1 therapy. Indeed, we have seen across our various studies that efti, with its unique mechanism of action, has the potential to benefit many cancer patients, including those with more limited treatment options."

PHASE II TACTI-002 POSTER PRESENTATION

Immutep's TACTI-002 is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of efti with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in 183 patients with non-small cell lung cancer (NSCLC) in 1st and 2nd line (Parts A and B, respectively) or 2nd line head and neck squamous cell carcinoma (HNSCC, Part C). The results announced today relate toPart C only.

Immutep CSO and CMO, Dr Frederic Triebel said: "It is encouraging to see deep and durable responses in low PD-L1expressing patients who may not typically respond to anti-PD-1therapy when given on its own. When given in combination with efti, we are seeing an ORR of about 30%. Results from TACTI-002demonstrate an encouraging ORR combined with a durable response and good safety. This was key to securing Fast Track Designation with the US FDA in April this year."

Key Findings 2nd line HNSCC - Part C

• ORR of 29.7% (11/37) per iRECIST in patients unselected for PD-L1 on an intention-to-treat basis and 35.5% (11/31) in evaluable patients
• 13.5% of patients (5/37) reporting a Complete Response, indicating deep responses
• Median duration of response is not yet reached and none of the patients with a confirmed response progressed within 9 months
• 5 patients still under therapy and 1 patient completed 2 years of therapy
• ORR in patients in the PD-L1 ≥ 1 (N = 27) and PD-L1 ≥ 20 (N = 14) subgroups is 40.7% and 64.3%, respectively

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Table 3 - TACTI-002 Interim ORR Results for Part C (data cut-off date: 4 August 2021)

			Part C
			2nd line HNSCC3
	Tumour Response		Stage 1 & 2
		N (%)
	Best Overall Response (BOR) per iRECIST
		Total N=37
	Complete Response (CR)	5 (13.5)
	Partial Response (PR)	6 (16.2)
	Stable Disease (SD)	3	(8.1)
	Progressive Disease (PD)	17	(45.9)
	Not Evaluable	6 (16.2)
	Disease Control Rate (DCR)	14	(37.8)
	Objective Response Rate (ORR)	11	(29.7)
	ORR in evaluable pts (N=31)	11	(35.5)

Conclusion: The more mature data from 2nd line HNSCC patients continues to be encouraging, including when compared to historical studies with checkpoint inhibitor monotherapy in comparable patient groups. These results are supportive of Immutep's randomised Phase IIb TACTI-003 study in the 1st line HNSCC indication conducted in collaboration with MSD. The trial design for the new TACTI-003 study isoutlined below.

Safety (data cut-off date 16 April 2021)

The combination treatment continues to be safe and well tolerated with no new safety signals reported thus far.

Next Results

Further data from TACTI-002 are planned to be reported in H1 of calendar year 2022.

PHASE II TACTI-003 POSTER PRESENTATION

TACTI-003 is a Phase IIb multicentre, open label, randomised and controlled, trial enrolling approximately 154 patients with 1st line HNSCC.

Patients will be enrolled into two cohorts (see Figure 5):

• Cohort A (approximately 130 patients) will evaluate the safety and efficacy of efti in combination with
  MSD's KEYTRUDA® (pembrolizumab), compared to pembrolizumab alone in 1st line metastatic or recurrent HNSCC patients with PD-L1 positive tumours (CPS ≥ 1).
• Cohort B (up to 24 patients) is an experimental arm which will determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumours (CPS < 1).

3 As assessed by local investigator read.

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