Upcoming SCIB1 data could provide first proof of concept
Update | 5 September 2023
Scancell has several key clinical data points due through to end-2024. First data will be from the Phase II trial of SCIB1 in combination with checkpoint inhibitors (CPIs) in advanced skin cancer. If successful the study will transition to the enhanced iSCIB1+ formulation that offers greater potency and broader applicability. If SCIB1 promising early data mature as hoped, then this programme could improve current outcomes. Top-line Modi-1 CPI combination data in multiple tumours are expected in 2024. The antibody platforms, GlyMab and AvidiMab, provide attractive out-licensing opportunities. Our Scancell rNPV valuation remains £300.1m, or 36.7p/share.
|Year-end: April 30||2021||2022||2023E||2024E|
|Adj. PBT (£m)||(17.7)||(11.9)||(17.6)||(24.0)|
|Net Income (£m)||(15.5)||(2.1)||(15.7)||(21.9)|
5 September 2023
|Shares in issue||818.4m|
|12 month range||8.05p-29.4p|
|Primary exchange||AIM London|
Scancell is a clinical-stage immuno-oncology specialist that has four broadly applicable technology platforms. Two are therapeutic vaccines, Moditope and ImmunoBody, and two are antibody based, GlyMab and AvidiMab.
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Scancell is a clinical stage immunology specialist. It has two promising oncology vaccine platforms, Moditope and ImmunoBody, and two antibody technologies, GlyMab (anti-glycans) and AvidiMab, with the potential to treat many solid cancers, either as monotherapy or in combination. Modi-1, the first Moditope programme, is progressing in a Phase I/II trial targeting hard-to-treat tumours with further efficacy data due 2024. The lead ImmunoBody programme, currently SCIB1, is in a Phase II study in metastatic melanoma, with a transition to the next-generation iSCIB1+ expected later this year. The broad acting GlyMab antibodies are generating exciting preclinical data, and a first partnering deal with Genmab is already in place and further deals are possible. AvidiMab technology will be increasingly employed to enhance avidity and potency. Our risk adjusted NPV valuation for Scancell is currently £300.1m, or 36.7p/share, with significant upside from multiple upcoming catalysts.
Scancell has four proprietary technology platforms, which can be classified into Vaccines (Moditope and ImmunoBody) and Antibodies (GlyMab and AvidiMab). More details on each are available in our February 2023 Outlook. Scancell’s pipeline of newsflow is summarised in Exhibit 1.
The lead ImmunoBody programme is currently SCIB1, which is being developed for the treatment of advanced melanoma. The open label Phase II SCOPE study is ongoing, which is examining SCIB1 in combination with checkpoint inhibitors (CPIs). Reflecting the changes in the treatment regimen for advanced metastatic melanoma, the focus is on the combination with doublet therapy, which consists of Bristol Myers Squibb’s Yervoy (ipilimumab) plus Opdivo (nivolumab).
The study rationale is that the SCIB1 ImmunoBody vaccine primes an immune response against the tumour, whilst the CPI reduces the immune-suppressant effect seen in the tumour microenvironment, which together could increase the number of patients who respond to treatment. Preclinical studies show a strong synergistic effect when SCIB1 is combined with a relevant CPI (c 85% response rates in animal models).
For context, and with the caveat of cross trial comparison limitations, the FDA approved label for Opdivo in combination with Yervoy, based on the CHECKMATE-067 study, cites an overall response rate (ORR) of 50% for the combination (based on a primary analysis with nine months of follow-up) vs 40% for Opdivo monotherapy and 14% for Yervoy alone. The ORR for the combination is 58% in longer-term CHECKMATE-067 data at both five and 6.5 years. Real-world data (at median follow-up of 12 months) reports an ORR of 48%. The ORRs achieved with doublet therapy are the highest observed in advanced melanoma.
Top-line data from the first stage (Cohort 1) of the SCOPE study, examining SCIB1 in combination with doublet therapy, are expected during Q423. This cohort will recruit up to 15 patients and a >55% response rate (ie nine responses) is required to validate the study hypothesis before progressing to the second stage. If nine responses are achieved in fewer than 15 patients, this would represent an ORR that appears higher than ORRs observed with doublet therapy alone, as described above. Hence, this could translate to improved outcomes for patients which would be a significant achievement, in our view.
The second stage will recruit up to a further 28 patients (for a total of up to 43 patients across both stages). The aim is to achieve 19 responses (ie 28 responses in total), which would represent at least a 65% response rate (28/43). This would demonstrate that SCIB1 in combination with doublet therapy exceeds currently achievable ORRs. Recruitment is expected to be complete by the end of 2023 with data around three months later ie during H124. If response rates of these magnitudes are achieved, then this could generate partnering interest, in our view.
The plan is to transition the SCOPE study to the enhanced, second-generation iSCIB1+. A repeat of Cohort 1 using iSCIB1+ in combination with doublet therapy could start by YE23 for top-line data H124e. If expanded data from these cohorts are positive, then a potentially registrational Phase II/III trial could be initiated.
The Phase I/II ModiFY study of Modi-1 is a two stage trial with an initial dose escalation and safety phase, already successfully completed, followed by a number of specific expansion cohorts that explore Modi-1 in a variety of hard-to-treat solid tumours as monotherapy, in combination with CPIs, as well as in the neoadjuvant (pre-surgical) setting. These include triple-negative breast cancer (TNBC), ovarian cancer, head & neck cancer, and renal cancer. A total of up to 138 patients across up to 20 UK sites will be treated. An overview of the trial design is shown in Exhibit 2.
The initial dose escalation and safety phase has been successfully completed with Modi-1 injections well tolerated at both low and high doses as monotherapy and in combination with a CPI. Recruitment into the ovarian cancer monotherapy cohort is complete, whilst recruitment into other expansion cohorts (monotherapy, combination with CPI, and neoadjuvant settings) is ongoing.
The ovarian cancer monotherapy expansion cohort has completed recruitment of 16 patients. All patients had failed prior treatment and had actively progressing disease. The disease control rate was 44% (7/16) following treatment with Modi-1 (stable disease for at least eight weeks), with some patients experiencing disease stabilisation for four or more months. In other monotherapy expansion cohorts, eight patients have received a full dose of Modi-1, with the following results:
Recruitment into the key CPI combination expansion cohorts has been approved and is underway, with data expected during 2024. These are focused on Modi-1 in combination with a CPI in head & neck and renal cancers, and in the neoadjuvant (pre-surgery) setting in head & neck cancer.
Scancell has built a pipeline of differentiated broad acting anticancer GlyMab antibodies, and currently has five in early-stage development. In October 2022 Genmab effectively validated the GlyMab platform when it acquired the rights to develop one of these preclinical antibodies, SC129, into multiple novel therapeutic product modalities for all disease areas, excluding cell therapy applications (which are retained by Scancell). The Genmab deal, which could generate up to a maximum of $624m in milestones if all the modalities were to be progressed, plus royalties, is an example of the partnering optionality within the GlyMab pipeline. We expect the remaining programmes, and other undisclosed ones in earlier stages of preclinical development, will be progressed to preclinical validation points and then also be partnered for further clinical development.
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