• |
KIMMTRAK (tebentafusp-tebn), our ImmTAC molecule targeting an HLA-A*02:01 gp100 antigen, is our first approved product. The FDA and the EC have approved KIMMTRAK
(tebentafusp-tebn and tebentafusp, respectively) for the treatment of HLA-A*02:01-positive adult patients with unresectable or mUM. KIMMTRAK demonstrated monotherapy activity and achieved the primary endpoint of superior overall survival in a
randomized Phase 3 clinical trial in patients with previously untreated mUM against the investigator’s choice of treatment. The OS Hazard Ratio, or HR, in the intent-to-treat population favored tebentafusp, HR=0.51 (95% CI: 0.37, 0.71); p<
0.0001, over investigator’s choice (82% pembrolizumab; 12% ipilimumab; 6% dacarbazine). The UK’s MHRA, Health Canada, and the Australian Government Department of Health’s TGA have each approved KIMMTRAK for the treatment of
HLA-A*02:01-positive adult patients with mUM.
|
• |
Tebentafusp is also being developed for the treatment of advanced melanoma. In June 2022, we presented updated clinical data from our Phase 1b clinical trial of KIMMTRAK
(tebentafusp) in metastatic cutaneous melanoma (mCM) in an oral presentation at the 2022 ASCO Annual Meeting. In combination with checkpoint inhibitors in mCM, the maximum target doses of tebentafusp (68 mcg) plus durvalumab (20 mg/kg) were
well tolerated. In mCM patients who progressed on prior anti-PD(L)1, tebentafusp with durvalumab continues to demonstrate promising overall survival (OS) (1-yr ~75%) compared to recent benchmarks (1-yr ~55%). We plan to conduct a randomized
Phase 2/3 clinical trial with and without an anti-PD(L)1 therapy. Our randomized trial will enroll patients with advanced melanoma that have progressed on an anti-PD1, received prior ipilimumab and, if applicable, received a tyrosine kinase
inhibitor (TKI). We are on track to start the Phase 2/3 clinical trial in the fourth quarter of 2022.
|
• |
IMC-F106C, our ImmTAC molecule targeting an optimal HLA-A*02:01 PRAME antigen is currently being evaluated in a first-in-human, Phase 1/2 dose
escalation clinical trial in patients with multiple solid tumor cancers including NSCLC, SCLC, endometrial, ovarian, cutaneous melanoma, and breast cancers. The initial Phase 1 data from the dose escalation study of IMC-F106C, the first
PRAME x CD3 ImmTAC bispecific protein, was presented as a proffered paper (oral presentation) during the “Investigational Immunotherapy” session at the 2022 European Society for Medical Oncology (ESMO) Congress. Durable RECIST responses and reduction in circulating tumor DNA (ctNDA) were observed across multiple solid tumors. Doses of ≥ 20 mcg were clinically active and had consistent and robust interferon gamma induction, a specific
marker of T cell activation. We have initiated patient enrollment into four expansion arms in cutaneous melanoma, ovarian, non-small cell lung cancer (NSCLC), and endometrial cancers. We will also study IMC-F106C in combination with
standards-of-care, including with tebentafusp.
|
• |
IMC-C103C, our ImmTAC molecule targeting an HLA-A*02:01 MAGE-A4 antigen, is currently being evaluated in a first-in-human, Phase 1/2 dose
escalation clinical trial in patients with solid tumor cancers. Data from the Phase 1 ovarian expansion arm of the dose escalation study with IMC-C103C, the MAGE-A4 x CD3 ImmTAC bispecific protein, was accepted for a poster presentation at
the ESMO Immuno-Oncology Congress 2022, in December. In this expansion arm, the Company enrolled all comers and evaluated MAGE expression retrospectively. In the initial dose escalation data reported at ESMO I-O in December 2021,
there were 15 response evaluable ovarian carcinoma patients in the active dose range (>=90 mcg). Only half were positive for MAGE-A4, with a median H score of 35 out of 300, and one patient had a confirmed partial response.
|
• |
IMC-I109V, our ImmTAV molecule targeting a conserved hepatitis B virus, or HBV, envelope antigen, is our most advanced ImmTAV program and is currently being evaluated in a
Phase 1/2 clinical trial in patients with chronic HBV who are non-cirrhotic, hepatitis B e-Antigen negative, and virally suppressed on chronic nucleot(s)ide analogue therapy. Our goal is to develop a functional cure for HBV. We reported
initial data from our trial in June 2022, observing a transient decrease in the HBV surface antigen, as well as transient elevations in alanine transaminase (“ALT”) and cytokines.
|
• |
IMC-M113V, our ImmTAV molecule targeting a human immunosuppression virus, or HIV, gag antigen bispecific TCR molecule, expected to be evaluated in a Phase 1/2 clinical trial
for which we are currently enrolling patients. Our goal is to develop a functional cure for HIV. We announced the dosing of the first patient in July 2022.
|
• |
we may face disruptions affecting the site initiation, patient enrollment, clinical trial site monitoring, development and operation of our clinical trials, including public health emergencies such as the
ongoing and evolving COVID-19 pandemic;
|
• |
after reviewing trial results, our collaboration partners may abandon projects that might previously have been believed to be promising;
|
• |
we, our collaboration partners, or regulators may suspend or terminate clinical trials if the participating subjects or patients are being exposed to unacceptable health risks;
|
• |
our potential products may not have the desired effects or may include undesirable side effects or other characteristics that preclude regulatory approval or limit their commercial use if approved;
|
• |
manufacturers may not meet the necessary standards for the production of the product candidates or may not be able to supply the product candidates in a sufficient quantity, including as a result of supply
chain disruptions caused by the COVID-19 pandemic and war in Ukraine and global geopolitical tensions;
|
• |
we may be unable to obtain additional funding necessary to continue our operations, including as a result of rising interest rates, credit and capital market instability and other impacts on global financial
markets of the ongoing COVID-19 pandemic, war in Ukraine, and global geopolitical tensions;
|
• |
we may face increased costs as a result of rising global inflation including significant increases in commodity prices, energy and fuel prices, and employee costs;
|
• |
regulatory authorities may find that our clinical trial design or conduct does not meet the applicable approval requirements; and
|
• |
safety and efficacy results in various human clinical trials reported in scientific and medical literature may not be indicative of results we obtain in our clinical trials.
|
Three Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
Product revenue, net
|
37,023
|
33,252
|
—
|
|||||||||
Pre-product, revenue, net
|
3,397
|
3,051
|
474
|
|||||||||
Total revenue from sale of therapies
|
40,420
|
36,303
|
474
|
|||||||||
Collaboration revenue
|
5,451
|
4,896
|
5,450
|
|||||||||
Total revenue
|
45,871
|
41,199
|
5,924
|
|||||||||
Cost of product revenue
|
(70
|
)
|
(63
|
)
|
—
|
|||||||
Research and development expenses
|
(25,943
|
)
|
(23,301
|
)
|
(16,798
|
)
|
||||||
Selling and administrative expenses
|
(12,986
|
)
|
(11,663
|
)
|
(20,048
|
)
|
||||||
Net other operating expense
|
—
|
—
|
(28
|
)
|
||||||||
Operating income / (loss)
|
6,872
|
6,172
|
(30,950
|
)
|
||||||||
Finance income
|
665
|
597
|
8
|
|||||||||
Finance costs
|
(1,987
|
)
|
(1,785
|
)
|
(1,317
|
)
|
||||||
Non-operating expense
|
(1,322
|
)
|
(1,188
|
)
|
(1,309
|
)
|
||||||
Profit / (loss) before taxes
|
5,550
|
4,984
|
(32,259
|
)
|
||||||||
Income tax credit
|
1,385
|
1,244
|
2,125
|
|||||||||
Profit / (loss) for the period
|
6,935
|
6,228
|
(30,134
|
)
|
Three Months Ended September 30, 2022
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
United States
|
25,061
|
22,508
|
—
|
|||||||||
Europe
|
14,512
|
13,034
|
474
|
|||||||||
Rest of World
|
847
|
761
|
—
|
|||||||||
Total revenue from sale of therapies
|
40,420
|
36,303
|
474
|
Three Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
GSK
|
—
|
—
|
1,263
|
|||||||||
Eli Lilly
|
—
|
—
|
—
|
|||||||||
Genentech
|
5,451
|
4,896
|
4,187
|
|||||||||
Total collaboration revenue
|
5,451
|
4,896
|
5,450
|
Three Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
External research and development expenses:
|
||||||||||||
Tebentafusp
|
3,839
|
3,448
|
4,649
|
|||||||||
IMC-F106C (PRAME)
|
4,603
|
4,134
|
1,715
|
|||||||||
IMC-C103C (MAGE-A4)
|
2,433
|
2,185
|
1,622
|
|||||||||
IMC-I109V(HBV)
|
228
|
205
|
75
|
|||||||||
IMC-M113V (HIV)
|
1,365
|
1,226
|
453
|
|||||||||
Other programs
|
2,131
|
1,914
|
1,372
|
|||||||||
Research expenses
|
186
|
167
|
93
|
|||||||||
Total external research and development expenses
|
14,785
|
13,279
|
9,979
|
|||||||||
Internal research and development expenses:
|
||||||||||||
Headcount related expenses
|
7,454
|
6,695
|
5,249
|
|||||||||
Laboratory consumables
|
2,387
|
2,144
|
995
|
|||||||||
Laboratory equipment expenses
|
1,158
|
1,040
|
559
|
|||||||||
Other
|
159
|
143
|
16
|
|||||||||
Total internal research and development expenses
|
11,158
|
10,022
|
6,819
|
|||||||||
Total research and development expenses
|
25,943
|
23,301
|
16,798
|
Three Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
Share-based payment charge
|
5,879
|
5,280
|
8,152
|
|||||||||
Other employee related expenses
|
7,060
|
6,341
|
3,945
|
|||||||||
Selling and commercial costs
|
8,320
|
7,472
|
5,077
|
|||||||||
Legal and professional fees
|
2,728
|
2,450
|
2,549
|
|||||||||
Depreciation
|
1,073
|
964
|
1,714
|
|||||||||
Other expenses
|
4,832
|
4,340
|
1,949
|
|||||||||
Foreign exchange gains
|
(16,906
|
)
|
(15,184
|
)
|
(3,338
|
)
|
||||||
Total selling and administrative expenses
|
12,986
|
11,663
|
20,048
|
Nine Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
Product revenue, net
|
72,289
|
64,926
|
—
|
|||||||||
Pre-product revenue, net
|
10,675
|
9,588
|
474
|
|||||||||
Total revenue from sale of therapies
|
82,964
|
74,514
|
474
|
|||||||||
Collaboration revenue
|
23,561
|
21,161
|
19,453
|
|||||||||
Total revenue
|
106,525
|
95,675
|
19,927
|
|||||||||
Cost of product revenue
|
(384
|
)
|
(345
|
)
|
—
|
|||||||
Research and development expenses
|
(69,066
|
)
|
(62,032
|
)
|
(53,154
|
)
|
||||||
Selling and administrative expenses
|
(56,316
|
)
|
(50,580
|
)
|
(64,033
|
)
|
||||||
Net other operating income / (expense)
|
1
|
1
|
(70
|
)
|
||||||||
Operating loss
|
(19,240
|
)
|
(17,281
|
)
|
(97,330
|
)
|
||||||
Finance income
|
807
|
725
|
42
|
|||||||||
Finance costs
|
(5,027
|
)
|
(4,515
|
)
|
(4,465
|
)
|
||||||
Non-operating expense
|
(4,220
|
)
|
(3,790
|
)
|
(4,423
|
)
|
||||||
Loss before taxes
|
(23,460
|
)
|
(21,071
|
)
|
(101,753
|
)
|
||||||
Income tax credit
|
5,623
|
5,050
|
9,619
|
|||||||||
Loss for the period
|
(17,837
|
)
|
(16,021
|
)
|
(92,134
|
)
|
Nine Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
United States
|
53,807
|
48,327
|
—
|
|||||||||
Europe
|
28,306
|
25,423
|
474
|
|||||||||
Rest of World
|
851
|
764
|
—
|
|||||||||
Total revenue from sale of therapies
|
82,964
|
74,514
|
474
|
Nine Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
£’000
|
|
£’000
|
||||||||
GSK
|
—
|
—
|
5,919
|
|||||||||
Eli Lilly
|
8,196
|
7,361
|
—
|
|||||||||
Genentech
|
15,365
|
13,800
|
13,534
|
|||||||||
Total collaboration revenue
|
23,561
|
21,161
|
19,453
|
Nine Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
|
£’000
|
|
£’000
|
|||||||
External research and development expenses:
|
||||||||||||
Tebentafusp
|
12,851
|
11,542
|
18,204
|
|||||||||
IMC-F106C (PRAME)
|
9,739
|
8,747
|
3,897
|
|||||||||
IMC-C103C (MAGE-A4)
|
6,286
|
5,646
|
3,569
|
|||||||||
IMC-I109V (HBV)
|
1,485
|
1,334
|
1,392
|
|||||||||
IMC-M113V (HIV)
|
2,474
|
2,222
|
909
|
|||||||||
Other programs
|
4,824
|
4,333
|
4,742
|
|||||||||
Research expenses
|
624
|
560
|
294
|
|||||||||
Total external research and development expenses
|
38,283
|
34,384
|
33,007
|
|||||||||
Internal research and development expenses:
|
||||||||||||
Headcount related expenses
|
21,504
|
19,314
|
15,747
|
|||||||||
Laboratory consumables
|
5,386
|
4,837
|
2,999
|
|||||||||
Laboratory equipment expenses
|
3,472
|
3,118
|
1,378
|
|||||||||
Other
|
421
|
379
|
23
|
|||||||||
Total internal research and development expenses
|
30,783
|
27,648
|
20,147
|
|||||||||
Total research and development expenses
|
69,066
|
62,032
|
53,154
|
Nine Months Ended September 30,
|
||||||||||||
2022
|
2021
|
|||||||||||
|
$’000
|
£’000
|
|
£’000
|
||||||||
Share-based payment charge
|
19,796
|
17,780
|
24,435
|
|||||||||
Other employee related expenses
|
17,064
|
15,326
|
10,850
|
|||||||||
Selling and commercial costs
|
24,815
|
22,287
|
11,168
|
|||||||||
Legal and professional fees
|
8,308
|
7,462
|
7,649
|
|||||||||
Depreciation
|
3,467
|
3,114
|
5,295
|
|||||||||
Other expenses
|
9,969
|
8,954
|
5,716
|
|||||||||
Foreign exchange gains
|
(27,103
|
)
|
(24,343
|
)
|
(1,080
|
)
|
||||||
Total selling and administrative expenses
|
56,316
|
50,580
|
64,033
|
Nine Months Ended September 30,
|
||||||||||||
2022
|
2022
|
2021
|
||||||||||
|
$’000
|
£’000
|
|
£’000
|
||||||||
Cash and cash equivalents at beginning of year
|
264,862
|
237,886
|
129,716
|
|||||||||
Net cash flows used in operating activities
|
(35,543
|
)
|
(31,923
|
)
|
(79,778
|
)
|
||||||
Net cash flows used in investing activities
|
(155
|
)
|
(139
|
)
|
(102
|
)
|
||||||
Net cash flows from financing activities
|
128,759
|
115,645
|
206,691
|
|||||||||
Net foreign exchange difference on cash
|
28,636
|
25,720
|
24
|
|||||||||
Cash and cash equivalents at end of period
|
386,559
|
347,189
|
256,551
|
• |
execute our sales and marketing strategy of KIMMTRAK in the United States, Europe and elsewhere;
|
• |
create additional infrastructure to support our operations as a public company listed in the United States and our product development and planned future commercialization efforts;
|
• |
continue to advance our clinical trials and the development of our pre-clinical programs;
|
• |
continue to invest in our soluble TCR platforms to conduct research to identify novel technologies;
|
• |
change or add additional suppliers;
|
• |
add additional infrastructure to our quality control, quality assurance, legal, compliance and other groups to support our operations as we progress product candidates toward commercialization;
|
• |
seek to attract and retain skilled personnel;
|
• |
seek marketing approvals and reimbursement for our product candidates;
|
• |
establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval;
|
• |
seek to identify and validate additional product candidates;
|
• |
acquire or in-license other product candidates and technologies;
|
• |
maintain, protect, defend, enforce and expand our intellectual property portfolio;
|
• |
encounter increased costs as a result of rising worsening macroeconomic conditions, including increased interest rates and rising global inflation;
|
• |
experience any supply chain or other disruptions, cost increases or other impacts of the war in Ukraine and global geopolitical tension; and
|
• |
experience any delays, interruptions or encounter issues with any of the above, including any delays or other impacts as a result of the ongoing and evolving COVID-19 pandemic.
|