Cantargia — Useful insights from CANOPY-1 data

Cantargia (OMX: CANTA)

Last close As at 25/12/2024

SEK2.35

0.01 (0.43%)

Market capitalisation

SEK510m

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Research: Healthcare

Cantargia — Useful insights from CANOPY-1 data

Novartis presented full results from its CANOPY-1 trial with canakinumab (anti-IL1beta; Cantargia’s CAN04 is an anti-IL1RAP with complete inhibition of IL-1) at the American Association for Cancer Research (AACR) Annual Meeting in April 2022. In our view one of the key findings was that patients with non-squamous non-small cell lung cancer (NSCLC) did better than those with squamous cancer types. This is beneficial for Cantargia, which already has a trial in non-squamous NSCLC underway. With regards to pancreatic cancer, the second lead indication, the company has now presented a plan for a registrational study. Multiple other catalysts are still due in the near term. Our valuation is SEK6.02bn or SEK60.1/share (from SEK68.9/share).

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Healthcare

Cantargia

Useful insights from CANOPY-1 data

Company update

Pharma & biotech

9 May 2022

Price

SEK12.5

Market cap

SEK1.25bn

Net cash and short-term investments (SEKm) at end-2021

559.4

Shares in issue

100.2m

Free float

99%

Code

CANT

Primary exchange

Nasdaq Stockholm

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

(32.5)

(34.8)

(59.4)

Rel (local)

(24.4)

(24.0)

(53.8)

52-week high/low

SEK33.1

SEK12.5

Business description

Cantargia is a clinical-stage biotechnology company based in Sweden, established in 2009. It is developing two assets against IL1RAP, CAN04 and CAN10. CAN04 is being studied in several solid tumours with a main focus on non-small cell lung cancer (NSCLC) and pancreatic cancer. The most advanced trial is in Phase II.

Next events

Updates from both Phase IIa CANFOUR trial arms (NSCLC and PDAC)

June 2022

Phase Ib CIRIFOUR first efficacy data

June 2022

Analysts

Jonas Peciulis

+44 (0)20 3077 5728

Soo Romanoff

+44 (0)20 3077 5700

Cantargia is a research client of Edison Investment Research Limited

Novartis presented full results from its CANOPY-1 trial with canakinumab (anti-IL1beta; Cantargia’s CAN04 is an anti-IL1RAP with complete inhibition of IL-1) at the American Association for Cancer Research (AACR) Annual Meeting in April 2022. In our view one of the key findings was that patients with non-squamous non-small cell lung cancer (NSCLC) did better than those with squamous cancer types. This is beneficial for Cantargia, which already has a trial in non-squamous NSCLC underway. With regards to pancreatic cancer, the second lead indication, the company has now presented a plan for a registrational study. Multiple other catalysts are still due in the near term. Our valuation is SEK6.02bn or SEK60.1/share (from SEK68.9/share).

Year end

Revenue (SEKm)

PBT*
(SEKm)

EPS*
(SEK)

DPS
(SEK)

P/E
(x)

Yield
(%)

12/20

0.0

(173.1)

(1.94)

0.0

N/A

N/A

12/21

0.0

(370.3)

(3.70)

0.0

N/A

N/A

12/22e

0.0

(368.5)

(3.68)

0.0

N/A

N/A

12/23e

0.0

(369.1)

(3.68)

0.0

N/A

N/A

Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.

Full CANOPY data provide insights for CAN04 strategy

Novartis had already reported that the CANOPY-1 trial had failed in October 2021, but the recently released subset analysis revealed several useful findings. In addition to differing outcomes depending on cancer histology, there were also some interesting data involving inflammatory markers. High sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6) level reductions were more pronounced in those patients who received Novartis’s canakinumab treatment. Those patients who had the largest reductions also had better outcomes. It appears that hs-CRP and IL-6 acted as prognostic factors, a finding that Cantargia can use in its trials.

Upcoming catalysts at ASCO

Following the R&D pipeline expansion, CAN04 is now being investigated in eight different cancers and different treatment lines and in a variety of combinations (Exhibit 2). This ensures plenty of catalysts to look forward to. The nearest significant event is the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on 3–7 June 2022. Cantargia will present three posters with a clinical data update from the lead Phase IIa CANFOUR trial (CAN04 plus chemotherapy in NSCLC and pancreatic cancer, which have been selected for discussion in a special session) and the first efficacy data from the Phase Ib CIRIFOUR trial (CAN04 plus pembrolizumab in solid tumours).

Valuation: SEK6.02bn or SEK60.1 per share

Our updated valuation of Cantargia is slightly lower at SEK6.02bn or SEK60.1 per share, versus SEK6.91bn or SEK68.9 per share previously (rolling our model forward was offset by a lower cash position). Cantargia’s registrational study in pancreatic cancer will be longer than we had modelled, which led us to delay the assumed launch date and licensing deal. This was partially offset by an increased probability of success and rolling the model forward.

Full Novartis Phase III CANOPY-1 results presented

As we have described several times before, canakinumab’s development has a complicated history and the read-across to Cantargia’s CAN04 is not straightforward. Canakinumab blocks only one of two cytokines that activate the IL-1 receptor, while Cantargia’s CAN04 completely abrogates the IL-1 signalling pathway. In addition, CAN04’s mechanism of action is not only inflammation modulation via IL1RAP, but also the antibody-dependent cellular cytotoxicity (ADCC), which directly causes cancer cell death. So, CANOPY studies provide valuable information of how to position CAN04, but do not invalidate the IL-1 axis theory in cancer, in our view.

As a reminder, on 25 October 2021, Novartis reported that the CANOPY-1 trial did not meet primary co-endpoints of overall survival (OS) and progression-free survival (PFS). The trial investigated canakinumab plus standard of care checkpoint inhibitor (pembrolizumab) and chemotherapy (platinum doublet) in first-line NSCLC patients. However, back then Novartis pointed out that the data showed ‘potentially clinically meaningful improvements’ in both co-primary endpoints in pre-specified subgroups of patients based on the baseline inflammatory biomarker. This, it believed, justified the continuation of other CANOPY trials, which are enrolling patients with even earlier-stage disease.

The most recent development was Novartis’s presentation of the full results from the CANOPY-1 trial at the AACR Annual Meeting in April 2022. The detailed results showed that the objective response rates were very similar in the canakinumab and placebo arms: 45.6% and 45.5%, respectively. The median PFS (co-primary endpoint) was 6.8 months for both treatment arms. The median OS (co-primary endpoint) was 20.8 months in the canakinumab arm and 20.2 months in the placebo arm.

The subset analysis revealed more interesting findings, which are relevant for Cantargia. In CANOPY-1 high sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6) level reductions were more pronounced in those patients who received the canakinumab combination treatment (Exhibit 1B). Those patients who had the largest reductions also had better and clinically meaningful improvements in both PFS and OS (Exhibit 1A; hs-CRP ranges expressed as quartiles, Q). It appears that hs-CRP and IL-6 acted as prognostic factors, a finding that will be useful for Cantargia in its trials as well. Furthermore, subgroup analysis revealed that patients with non-squamous cancer did better than those with squamous cancer (Exhibit 1C).

The CRP test is the most common inflammatory biomarker to evaluate an active infection used in the clinic (the hsCRP test simply measures much smaller amounts of the same protein in seemingly healthy persons; one is used to estimate the risk of heart disease for example). Minimal signs of ongoing inflammation in the background could potentially be used as a biomarker to identify a more relevant subgroup of patients. This would make sense given the mechanism of action of canakinumab (anti-IL1β, which diminishes pro-inflammatory IL-1 signalling) or CAN04 (anti-IL1RAP, which abrogates signalling via IL-1).

Exhibit 1:Selected data from Novartis’s CANOPY-1 trial

Source: Novartis

Cantargia’s focus on non-squamous NSCLC

Cantargia’s focus shifted to non-squamous NSCLC well before Novartis released its CANOPY-1 data. As we discussed in our last report, Cantargia presented the latest interim results from the NSCLC arm of the CANFOUR trial at the ESMO Congress in September 2021. It was not the first data update from this trial and the encouraging overall response rates (ORR) tracked those reported previously. The new and unexpected finding was that a subset of patients who had non-squamous NSCLC showed a more pronounced benefit compared to those with squamous histology. Based on this finding, Cantargia decided to focus on further development in non-squamous NSCLC, which is the largest subgroup of NSCLC and constitutes about 70–80% of all NSCLC cases. Cantargia initiated a new trial within the CANFOUR programme, which has started enrolling patients with non-squamous NSCLC for front-line treatment with CAN04 in combination with carboplatin/pemetrexed. In total, 40 new patients are planned to be recruited.

Other R&D developments

A detailed review of Cantargia’s expanded R&D pipeline was presented in our last report. Since then, major developments include:

Cantargia announced updated survival data from its CANFOUR trial with nadunolimab and chemotherapy in metastatic pancreatic cancer (n=36, of which 33 were evaluable). This is first-line treatment setting with patients receiving standard of care chemotherapy gemcitabine/nab-paclitaxel (around 50% of all pancreatic cancer patients receive it). Interim response data have been published on several occasions previously and compared very well with historical control data. The new update is in line with the previously published findings and strengthens the conviction in this indication, in our view, which is reassuring given Cantargia is currently preparing for a randomised and potentially pivotal trial in first-line pancreatic cancer. The next update from the pancreatic cancer arm of the CANFOUR study will be presented at ASCO in June 2022.

Earlier this year, Cantargia initiated a collaboration with the Pancreatic Cancer Action Network (PanCAN), a US organisation. Nadunolimab will be included in PanCAN’s ongoing Phase II/III clinical trial Precision Promise, which is a potentially registrational trial. The primary endpoint in this trial is OS. PanCAN plans to submit a pre-IND application to the FDA in H122 to include the nadunolimab treatment arm as an experimental arm in the Precision Promise trial, which also has other experimental arms. Each arm will enrol up to 175 patients. Nadunolimab will be combined with gemcitabine and nab-paclitaxel, or a standard of care chemotherapy regime alone. The study should start in late 2022 and the results for the nadunolimab arm are expected to be available in 2027 or earlier. Cantargia will fund the nadunolimab arm and will be responsible for supplying the drug, while PanCAN will fund the reminder of the trial, which makes it a cost-efficient strategy for Cantargia.

Exhibit 2: R&D pipeline

Source: Cantargia

Financials and valuation

In 2021, Cantargia reported an increased operating loss of SEK370m (FY20: SEK174m), driven by the growing R&D costs. We had already anticipated growing R&D costs. Following the latest results, we have extended our 2022 operating loss estimate somewhat, to SEK369m from SEK349m previously, and keep the spending similar in 2023. Existing cash and short-term investments (SEK559m at end-2021) are still sufficient well into 2023.

Our updated valuation of Cantargia is slightly lower at SEK6.02bn or SEK60.1 per share, versus SEK6.91bn or SEK68.9 per share previously, as rolling our model forward was offset by a lower cash position. This was a result of several changes to our model. We have delayed the assumed launch of CAN04 in pancreatic cancer to 2027 from 2024 now that Cantargia has communicated its registrational trial plans.

In our base case valuation we assume a licensing deal for both indications, which we delay now to 2024 from 2023. A full out-licensing deal, as explained in our initiation report, is a theoretical component of our model. In reality, there could be various arrangements from out-licensing to co-development or Cantargia could complete the development of CAN04 in pancreatic cancer on its own. We have also increased the success probability in the pancreatic cancer project to 40% from 25%, which is in line with historical success probabilities in Phase III, and we have rolled the model forward, which has partially offset the delays.

Exhibit 3: Sum-of-the-parts Cantargia valuation

Product

Launch

Peak sales
($m)

NPV
(SEKm)

NPV/share (SEK)

Probability

rNPV
(SEKm)

rNPV/share
(SEK)

CAN04 – NSCLC

2026

3,100

9,240.2

92.2

25.0%

2,620.0

26.1

CAN04 – PDAC

2027

2,124

6,504.6

64.9

40.0%

2,845.1

28.4

Net cash* (last reported)

559.4

5.6

100%

559.4

5.6

Valuation

16,304.2

162.7

6,024.5

60.1

Source: Edison Investment Research. Note: WACC = 12.5% for product valuations. *Including short-term investments.

Exhibit 4: Financial summary

SEK'000s

2019

2020

2021

2022e

2023e

Year end 31 December

IFRS

IFRS

IFRS

IFRS

IFRS

PROFIT & LOSS

Revenue

 

 

0

0

0

0

0

Cost of Sales

0

0

0

0

0

Gross Profit

0

0

0

0

0

Research and development

(97,477)

(158,396)

(352,709)

(350,000)

(350,000)

EBITDA

 

 

(111,577)

(170,697)

(366,821)

(365,101)

(365,657)

Operating Profit (before amort. and except.)

 

 

(111,589)

(173,945)

(370,267)

(368,547)

(369,103)

Intangible Amortisation

0

0

0

0

0

Exceptionals

0

0

0

0

0

Other

0

0

0

0

0

Operating Profit

(111,589)

(173,945)

(370,267)

(368,547)

(369,103)

Net Interest

780

860

0

0

0

Profit Before Tax (norm)

 

 

(110,809)

(173,085)

(370,267)

(368,547)

(369,103)

Profit Before Tax (reported)

 

 

(110,809)

(173,085)

(370,267)

(368,547)

(369,103)

Tax

0

0

0

0

0

Profit After Tax (norm)

(110,809)

(173,085)

(370,267)

(368,547)

(369,103)

Profit After Tax (reported)

(110,809)

(173,085)

(370,267)

(368,547)

(369,103)

Average Number of Shares Outstanding (m)

71.1

89.4

100.2

100.2

100.2

EPS - normalised (SEK)

 

 

(1.56)

(1.94)

(3.70)

(3.68)

(3.68)

Dividend per share (SEK)

0.0

0.0

0.0

0.0

0.0

Gross Margin (%)

N/A

N/A

N/A

N/A

N/A

EBITDA Margin (%)

N/A

N/A

N/A

N/A

N/A

Operating Margin (before GW and except.) (%)

N/A

N/A

N/A

N/A

N/A

BALANCE SHEET

Fixed Assets

 

 

6,868

12,622

9,556

9,556

9,556

Intangible Assets

0

7,360

6,459

6,459

6,459

Tangible Assets

6,868

5,262

3,097

3,097

3,097

Investments

0

0

0

0

0

Current Assets

 

 

159,189

912,892

590,687

230,679

31,301

Stocks

0

0

0

0

0

Debtors

0

0

0

0

0

Cash

39,870

693,354

247,322

199,378

0

Other*

119,319

219,538

343,365

31,301

31,301

Current Liabilities

 

 

(23,785)

(30,469)

(66,607)

(66,607)

(66,607)

Creditors

(23,785)

(30,469)

(66,607)

(66,607)

(66,607)

Short term borrowings

0

0

0

0

0

Long Term Liabilities

 

 

0

(3,111)

(892)

(892)

(162,076)

Long term borrowings

0

0

0

0

(161,184)

Other long term liabilities

0

(3,111)

(892)

(892)

(892)

Net Assets

 

 

142,272

891,934

532,744

172,736

(187,826)

CASH FLOW

Operating Cash Flow

 

 

(111,852)

(156,887)

(347,370)

(360,006)

(360,562)

Net Interest

597

500

924

0

0

Tax

0

0

0

0

0

Capex

(6,880)

(890)

0

0

0

Acquisitions/disposals

0

0

0

0

0

Financing

98,037

917,545

0

(320)

(317)

Other (incl. change in short term investments)

(16,560)

(106,784)

(99,586)

312,381

317

Dividends

0

0

0

0

0

Net Cash Flow

(36,658)

653,484

(446,032)

(47,944)

(360,562)

Opening net debt/(cash)

 

 

(76,528)

(39,870)

(693,354)

(247,322)

(199,378)

HP finance leases initiated

0

0

0

0

0

Other

0

0

0

0

0

Closing net debt/(cash)

 

 

(39,870)

(693,354)

(247,322)

(199,378)

161,184

Source: Cantargia accounts, Edison Investment Research. Note: *Mainly short-term investments.


General disclaimer and copyright

This report has been commissioned by Cantargia and prepared and issued by Edison, in consideration of a fee payable by Cantargia. Edison Investment Research standard fees are £60,000 pa for the production and broad dissemination of a detailed note (Outlook) following by regular (typically quarterly) update notes. Fees are paid upfront in cash without recourse. Edison may seek additional fees for the provision of roadshows and related IR services for the client but does not get remunerated for any investment banking services. We never take payment in stock, options or warrants for any of our services.

Accuracy of content: All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report and have not sought for this information to be independently verified. Opinions contained in this report represent those of the research department of Edison at the time of publication. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations.

Exclusion of Liability: To the fullest extent allowed by law, Edison shall not be liable for any direct, indirect or consequential losses, loss of profits, damages, costs or expenses incurred or suffered by you arising out or in connection with the access to, use of or reliance on any information contained on this note.

No personalised advice: The information that we provide should not be construed in any manner whatsoever as, personalised advice. Also, the information provided by us should not be construed by any subscriber or prospective subscriber as Edison’s solicitation to effect, or attempt to effect, any transaction in a security. The securities described in the report may not be eligible for sale in all jurisdictions or to certain categories of investors.

Investment in securities mentioned: Edison has a restrictive policy relating to personal dealing and conflicts of interest. Edison Group does not conduct any investment business and, accordingly, does not itself hold any positions in the securities mentioned in this report. However, the respective directors, officers, employees and contractors of Edison may have a position in any or related securities mentioned in this report, subject to Edison's policies on personal dealing and conflicts of interest.

Copyright: Copyright 2022 Edison Investment Research Limited (Edison).

Australia

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New Zealand

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United Kingdom

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General disclaimer and copyright

This report has been commissioned by Cantargia and prepared and issued by Edison, in consideration of a fee payable by Cantargia. Edison Investment Research standard fees are £60,000 pa for the production and broad dissemination of a detailed note (Outlook) following by regular (typically quarterly) update notes. Fees are paid upfront in cash without recourse. Edison may seek additional fees for the provision of roadshows and related IR services for the client but does not get remunerated for any investment banking services. We never take payment in stock, options or warrants for any of our services.

Accuracy of content: All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report and have not sought for this information to be independently verified. Opinions contained in this report represent those of the research department of Edison at the time of publication. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations.

Exclusion of Liability: To the fullest extent allowed by law, Edison shall not be liable for any direct, indirect or consequential losses, loss of profits, damages, costs or expenses incurred or suffered by you arising out or in connection with the access to, use of or reliance on any information contained on this note.

No personalised advice: The information that we provide should not be construed in any manner whatsoever as, personalised advice. Also, the information provided by us should not be construed by any subscriber or prospective subscriber as Edison’s solicitation to effect, or attempt to effect, any transaction in a security. The securities described in the report may not be eligible for sale in all jurisdictions or to certain categories of investors.

Investment in securities mentioned: Edison has a restrictive policy relating to personal dealing and conflicts of interest. Edison Group does not conduct any investment business and, accordingly, does not itself hold any positions in the securities mentioned in this report. However, the respective directors, officers, employees and contractors of Edison may have a position in any or related securities mentioned in this report, subject to Edison's policies on personal dealing and conflicts of interest.

Copyright: Copyright 2022 Edison Investment Research Limited (Edison).

Australia

Edison Investment Research Pty Ltd (Edison AU) is the Australian subsidiary of Edison. Edison AU is a Corporate Authorised Representative (1252501) of Crown Wealth Group Pty Ltd who holds an Australian Financial Services Licence (Number: 494274). This research is issued in Australia by Edison AU and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. Any advice given by Edison AU is general advice only and does not take into account your personal circumstances, needs or objectives. You should, before acting on this advice, consider the appropriateness of the advice, having regard to your objectives, financial situation and needs. If our advice relates to the acquisition, or possible acquisition, of a particular financial product you should read any relevant Product Disclosure Statement or like instrument.

New Zealand

The research in this document is intended for New Zealand resident professional financial advisers or brokers (for use in their roles as financial advisers or brokers) and habitual investors who are “wholesale clients” for the purpose of the Financial Advisers Act 2008 (FAA) (as described in sections 5(c) (1)(a), (b) and (c) of the FAA). This is not a solicitation or inducement to buy, sell, subscribe, or underwrite any securities mentioned or in the topic of this document. For the purpose of the FAA, the content of this report is of a general nature, is intended as a source of general information only and is not intended to constitute a recommendation or opinion in relation to acquiring or disposing (including refraining from acquiring or disposing) of securities. The distribution of this document is not a “personalised service” and, to the extent that it contains any financial advice, is intended only as a “class service” provided by Edison within the meaning of the FAA (i.e. without taking into account the particular financial situation or goals of any person). As such, it should not be relied upon in making an investment decision.

United Kingdom

This document is prepared and provided by Edison for information purposes only and should not be construed as an offer or solicitation for investment in any securities mentioned or in the topic of this document. A marketing communication under FCA Rules, this document has not been prepared in accordance with the legal requirements designed to promote the independence of investment research and is not subject to any prohibition on dealing ahead of the dissemination of investment research.

This Communication is being distributed in the United Kingdom and is directed only at (i) persons having professional experience in matters relating to investments, i.e. investment professionals within the meaning of Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "FPO") (ii) high net-worth companies, unincorporated associations or other bodies within the meaning of Article 49 of the FPO and (iii) persons to whom it is otherwise lawful to distribute it. The investment or investment activity to which this document relates is available only to such persons. It is not intended that this document be distributed or passed on, directly or indirectly, to any other class of persons and in any event and under no circumstances should persons of any other description rely on or act upon the contents of this document.

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Research: TMT

CLIQ Digital — Momentum continuing unabated

CLIQ Digital (CLIQ) has had a positive start to the year, with Q122 results providing an early indication that it is on track to meet its guidance for strong growth and increased profitability in FY22. Its shift to direct media buying continues to drive rapid growth in the membership base in North America and Europe, with more members now choosing to pay for its multi-content offering. This reflects the success to date of investments in marketing and new content. As expected and guided, the additional spend will depress EBITDA margin in the current year, but we would expect it to start to rebuild in FY23.

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