Vantage Snippets are short summaries of breaking news stories.
Such is the appetite for biotech stocks at present that trading below cash, and 75% below your IPO price, is apparently no barrier to tapping investors for more cash. A case in point is Mereo, which yesterday closed a $70m private placement led by Orbimed, largely on the strength of its pipeline containing the anti-Tigit MAb etigilimab, whose mechanism has generated interest from Roche and Merck & Co. In late 2020, having sat on the shelf for nearly two years since coming to Mereo via the takeover of Oncomed, etigilimab will start a new phase I trial, though the design has yet to be decided. In April the private Belgian Tigit player Iteos raised $125m. The little clinical data available on etigilimab (earlier coded OMP-313M32) appear unconvincing, with stable disease being the best result in an Oncomed-sponsored dose-escalation trial now marked “terminated” on clinicaltrials.gov. The project had been optioned to Celgene, which declined to exercise this, though the decision might have been due to its takeover by Bristol-Myers Squibb. Despite the red flags and resulting dilution, Mereo’s raise has been seen as a new lease of life, and the shares closed up 56% yesterday.
Whether yesterday’s deals with Medtronic pull Titan Medical out of the pit into which it has fallen is an open question, but it does at least give the distressed robotic surgery group a leg up. The first deal will see the partners development robotic surgical tech for use in their respective businesses. Medtronic will make milestone payments totalling $31m to license Titan’s tech; one of these is dependent on Titan raising an additional $18m within the next five months. Titan has also borrowed $1.5m at 8% per annum from Medtronic, and intends to borrow more to pay legal expenses. A separate agreement is a straight-up licence under which Medtronic gains access to some of Titan’s existing tech for $10m up front. Medtronic will presumably use its new machinery or software to aid development of its Hugo surgical robot; this was also the reasoning behind its acquisition, for an undisclosed amount, of the UK group Digital Surgery in February. Titan, meanwhile, escapes having to delist from Nasdaq. Its shares rose 463% yesterday, though the market cap is still below $100m. If Titan cannot meet its obligations perhaps Medtronic will buy it up – doubtless for a knockdown price.
Having recently proven itself in the randomised withdrawal setting, Novo Nordisk’s semaglutide has repeated the trick in a direct comparison against placebo. The Step 1 study has shown a 2.4mg daily dose of the GLP-1 agonist in its anti-obesity incarnation to deliver a knockout level of weight loss after 68 weeks’ treatment: 14.9% versus baseline, or 12.5% adjusted for weight loss seen in the placebo cohort. Last month the Step 4 study read out, showing 68-week weight loss of 17.4% from baseline. That trial had a randomised withdrawal design, with the first 20 weeks being on semaglutide before a 48-week placebo-controlled stage, during which placebo recipients regained an average 6.6kg of the 11.1kg they had lost during the run-in. At 1,950 subjects Step 1 is the biggest of Novo’s four pivotal studies reading out this year. Sellside consensus from EvaluatePharma shows 2026 forecast revenues of $1.7bn coming from semaglutide’s obesity use, with the vast majority of the remaining $12.3bn coming from its approved indication of type 2 diabetes. Historically obesity drugs have been scuppered by poor efficacy or unacceptable toxicity, and more on semaglutide’s “gastrointestinal events” is needed before declaring the Novo project an unequivocal winner.
|2020 obesity readouts for Novo Nordisk's semaglutide/Ozempic|
|Clinical study||Study details||Data|
|Step 4 (NCT03548987)||Maintaining weight loss: randomised withdrawal study (n=900)||At 20 weeks (sema run-in): 10.4% weight loss
After further 48 weeks: further 7.9% weight loss, vs 6.9% weight gain for placebo
|Step 1 (NCT03548935)||Weight management: semaglutide 2.4mg vs placebo (n=1,950)||At 68 weeks: 14.9% weight loss, vs 2.4% for placebo; ≥5% weight loss achieved by 92.4% of sema patients, vs 33.1% for placebo|
|Step 2 (NCT03552757)||Weight management in type 2 diabetes: semaglutide 1mg & 2.4mg vs placebo (n=1,200)||Expected|
|Step 3 (NCT03611582)||Maximising weight loss: semaglutide 2.4mg + intensive behavioural therapy vs placebo (n=600)||Expected|
Approval of the repurposed cancer drug Arzerra (ofatumumab), which Novartis has flipped into multiple sclerosis, was slated as one of June’s biggest FDA decisions. That verdict is now delayed to September, the Swiss pharma giant said this week, without providing a reason. Issues with the filing could be responsible; however, it is notable that the agency recently issued new guidance warning that PDUFA and BsUFA goals and timelines might be hit in the coming months. A considerable increase in Covid-19-related work has strained resources, which might have to be focused on applications relating to pandemic-specific treatments or other life-threatening conditions, the FDA said. It is pretty surprising that drug approvals have so far been unaffected, and investors should perhaps brace for delays in the coming months; though infections in the US do seem to be declining, it is clear that the situation in the country remains precarious. Whatever the reason for the ofatumumab delay Novartis will still hope for a green light later this year. The project, which has been reformulated for subcutaneous delivery, is pegged as the company’s most important sales growth driver over the coming years, according to sellside consensus data from EvaluatePharma.
Inovio investors were rattled this week by reports that the company was no longer in consideration for the White House’s “Project Warp Speed”. Executives at Glaxosmithkline and Sanofi were probably feeling the burn of rejection more keenly. The US government-backed programme is seeking a Covid-19 vaccine to accelerate with cash and expertise; according to the New York Times five candidates remain in the running, with the finalist due to be selected soon. Inovio is a tiny player whereas Sanofi and Glaxo are two of the world’s biggest vaccine makers. Glaxo in particular must be smarting: Warp Speed’s chief adviser is Moncef Slaoui, who worked at the UK pharma giant for decades, and for a time led its vaccine arm. True, neither of the two companies’ candidates, one of which is being developed jointly, has yet reached the clinic, but then nor has any from Merck, which only entered the game last month. The combined scale of these apparently snubbed operators makes their efforts hard to overlook, particularly when newcomer Moderna made the cut; Mr Slaoui has also served as a board member here. With Bloomberg now reporting that another two unnamed companies are in fact on the shortlist, perhaps a wrong has been hurriedly righted.
|Travelling at warp speed? The five Covid-19 vaccine players shortlisted, and other clinical candidates|
|Reported as selected for Project Warp Speed|
|Uni of Oxford/ Astrazeneca||AZD1222 (COV001)||Chimp adenovirus vaccine||Data from 1,100-patient trial expected imminently|
|Moderna/NIAID/Cepi||mRNA-1273||mRNA vaccine||Small amount of phase I data released; phase II trial recruiting|
|Biontech/Pfizer||BNT162||mRNA vaccine||First cohorts dosed in phase I/II trial|
|Johnson & Johnson||No product code||Adenovirus type 26 vaccine||Phase I to start Sep 2020|
|Merck/Themis||No product code||Measles virus vector vaccine||Clinical studies to start later this year|
|Other clinical stage projects, not on the list|
|Inovio||INO-4800||DNA vaccine||Enrolment in phase I trial complete, results expected Jun; phase II/III planned in summer|
|Cansino/Academy of Military Medical Sciences||Ad5-nCoV||Adenovirus type 5 vaccine||China study under way|
|Shenzhen Genoimmune||LV-SMENP-DC||Synthetic minigene vaccine||Clinical trial started Mar 2020|
|Sinovac||CoronaVac||Inactivated SARS-CoV-2 vaccine||Phase I trial recruiting in China|
|Source: EvaluatePharma & company statements.|
Gilead’s $375m tie-up with Arcus last week put the spotlight back on anti-Tigit antibodies, where Roche’s tiragolumab looks to be in the lead. Roche’s updated Asco presentation over the weekend of tiragolumab’s Cityscape trial in first-line NSCLC thus generated interest, though perhaps of even greater relevance were the Swiss firm’s plans for tiragolumab. When Cityscape’s abstract dropped the efficacy of the Tecentriq monotherapy comparator arm looked low, but at Asco Roche stressed that this concerned 5.9 months’ median follow-up; at 10.9 months the remission rate goes up in the tiragolumab combo and monotherapy arms alike, because numerous unconfirmed remissions have by then been confirmed. The efficacy is especially striking in ≥50% PD-L1 expressers, though a 24% response rate for Tecentriq monotherapy in this group still underperforms the 29% seen in the Impower-110 trial. Roche accepted that Tigit blockade offered little hope as monotherapy, but presented mechanistic data suggesting a role for the mechanism as a key element of an anti-PD-(L)1 combo. However, its Tigit combo also lacks efficacy in low PD-L1 expressers, clouding the commercial opportunity. An NSCLC cohort from tiragolumab’s phase I solid tumour trial will feature at an AACR meeting plenary session on June 23.
The last few days have seen the FDA grant emergency authorisation to four novel Covid-19 tests, two of which are for Siemens Healthineers’ total antibody test. One of the test’s EUAs permits it to be run on the Atellica immunoassay analyser, which can run up to 440 tests per hour and return a result in 10 minutes, the German group says; the other covers the test when it is run on the Advia Centaur range of systems. Healthineers’ claims for the accuracy of these tests are on a par with those made by Roche and Abbott for their respective antibody tests. Healthineers has already shipped a million tests and says it has capacity to produce more than 50 million per month. Of these three groups Abbott was first to market with the launch of its antibody test on April 15, giving it a six-week advantage over Healthineers. Separately, the FDA bestowed an EUA on another home-use kit for detecting nucleic acid from the coronavirus in self-collected nasal swab specimens. The LetsGetChecked kit, sold by Privapath Diagnostics, offers results within 24 hours.
|Accuracy figures for selected Covid-19 antibody tests sold in the US|
|Company||Test name||Date of US EUA||EU status||Sensitivity or PPA (%)||Specificity or NPA (%)|
|Siemens Healthineers||Atellica IM Sars-CoV-2 Total (COV2T)||May 29||CE marked||100*||99.8|
|Siemens Healthineers||Advia Centaur Sars-CoV-2 Total (COV2T)||May 29||CE marked||100*||99.8|
|Roche||Elecsys anti-Sars-CoV-2 antibody test||May 2||CE marked||100*||99.8|
|Abbott Laboratories||Abbott Sars-CoV-2 IgG test||Apr 26||CE marked||100**||99.5|
|*at >14 days post PCR confirmation of disease. **at >14 days post symptom onset. Source: FDA.|
The Asco starting gun fired up Adaptimmune this morning, with shares in the UK cell therapy company almost doubling. After years of glacial movement the developer’s engineered T-cell receptor projects now appear to be making progress, and a stake has been put in the ground regarding first launch: 2022, for ADP-A2M4 in synovial sarcoma. New data at Asco on the Mage-A4-targeted therapy include a 50% (8/16) response rate in this cancer, although this includes one unconfirmed partial remission recorded after data cut-off. Still, evidence that these responses are durable is emerging, to the extent that Adaptimmune now considers the Spearhead-1 trial registrational, though whether this has been agreed by regulators is not immediately clear. In a prerecorded presentation executives said interactions with agencies had been "productive and supportive”. Press-released data, not scheduled for Asco, also helped give the stock a boost. Three of four patients treated with Adaptimmune's next-gen Mage-A4 project ADP-A2M4CD8 have responded, while a separate AFP-targeted therapy, ADP-A2AFP, achieved a complete response in liver cancer. Three other patients treated with ADP-A2AFP failed to respond, but it seems that today Adaptimmune investors are focusing on the positives.
|Finally making progress? Adaptimmune's Asco update|
|Project (target)||Trial||January update||Asco clinical update||Asco strategy update|
|ADP-A2M4 (Mage-A4)||Spearhead-1||-||44% ORR in synovial sarcoma, mDOR 28 weeks.||Trial to become registrational for sarcoma; targeting launch 2022|
|Multi-tumour trial||2 PRs (1 unconfirmed) in rectal mucosal melanoma & H&N cancer||1 new confirmed PR in lung cancer|
|Spearhead-2||Trial in combination with Keytruda in H&N to start later this year|
|ADP-A2M4CD8 (Mage-A4)||Surpass||1 PR (unconfirmed) in EGJ||Previous EGJ PR ongoing at 6 months; additional unconfirmed PRs in EGJ and H&N; 1 non-response||Trial to focus on lung, EGJ, H&N and bladder cancers; data to be presented in H2|
|Trial in EGJ planned for H1 2021|
|ADP-A2AFP (Alpha-fetoprotein)||NCT03132792||1 confirmed PR in liver cancer||Liver PR converted to CR, ongoing at week 24; 3 further non-responders, 2 in HCC||Data to be presented at ILC in August 2020|
|PR = partial response. CR = complete response. EGJ = oesophagogastric junction cancer. H&N = head & neck. Source: company press release.|
The final overall survival analysis of Aveo Oncology’s Tivo-3 trial of its VEGF inhibitor tivozanib has yielded deeply unconvincing results. The trial, comparing tivozanib versus Nexavar in third-line renal cell carcinoma, has come up with a hazard ratio of 0.97 according to data presented at Asco today. This is a sliver better than November’s 0.99 interim figure, which was in turn an uptick from the initial 1.12 reported last July. The crucial point, however, is that median OS favours Nexavar, the figures at the final analysis being 16.4 months for tivozanib and 19.2 months for Bayer’s drug. The data have been added to Aveo’s US regulatory filing, with the company presumably hoping that the late separation in the survival curves, along with the hit on progression-free survival, might persuade the FDA to give its blessing. A potential FDA rejection is only one cloud on the horizon: previously the EMA has said it might consider pulling the drug off the European market should Tivo-3’s final OS analysis come out negative. Perhaps it is this threat that has scared off investors: Aveo’s stock is down 14% in early trade.
Early results with the second of Mersana Therapeutics’ antibody-drug conjugates to enter the clinic lifted the company’s stock 69% yesterday; despite the data coming from only a handful of patients they are apparently strong enough to justify a $700m uplift in valuation. XMT-1536 is an ADC directed at NaPi2b, which is expressed in a high proportion of certain lung and ovarian cancers. Mersana is recruiting subjects with both of these tumour types into a phase I study. Data in 20 patients with heavily pretreated platinum-resistant ovarian cancer were disclosed, XMT-1536 achieving a 35% remission rate, including two confirmed complete responses and five partial responses. More data are needed in NSCLC, the company said, with little activity seen in seven patients. While this is encouraging, long-term durability of responses remains an important unknown; Roche abandoned an NaPi2b-targeted ADC, RG7599, a couple of years ago after this failed to help patients for long, despite bestowing a similar ORR. Still, after Mersana scrapped a Her2-targeted ADC last year these results appear to have given it a second chance, and the company wasted no time raising money, announcing an equity offering this morning that should net around $100m.