Respirator drug candidate VAL001 is being developed for the treatment of diffuse large B-cell lymphoma (DLBCL). DLBCL is a rare and aggressive form of lymph node cancer and the most common type of Non-Hodgkin's Lymphoma (NHL), with DLBCL accounting for around 30 percent of cases. Today's standard treatment consists of R-CHOP, a combination treatment that includes both chemotherapy and the antibody-based drug Rituxan (rituximab).
However, the treatment outcome of this combination therapy is suboptimal with a 5-year survival of approximately 60-70 percent, which opens the door to new therapies such as VAL001.
Strong survival data
In 2018, Respiratorius was able to publish a article in the highly ranked scientific journal of the American Society of Hematology – Blood advances – which showed that the overall 1-year survival was 100 percent for the 32 patients treated with VAL001 and R-CHOP. The 2-year survival, which is an even more important outcome measure because it often translates to the disease being cured, was a whopping 96,8 percent. Comparative data from a matched reference population from the Swedish Lymphoma Registry treated with R-CHOP alone showed a 1-year survival of 89,6 percent and a 2-year survival of 81,7 percent.
VAL001 has also been shown to reduce the risk of mortality – the risk of dying in DLBCL – by 80 percent compared to standard treatment. This result is striking considering that mortality reductions of 20–30 percent are considered a clinically relevant improvement.
Overall, the results demonstrate a statistically significant survival advantage for patients treated with VAL001 and R-CHOP compared to patients treated with R-CHOP alone between 2000 and 2015.
The goal is to initiate a partnership for the phase III study
Now there are only a few steps left before the next stage of development work with the candidate can take place, that is, a phase III study. First, a pharmacokinetic study will be conducted and secondly, a study protocol will be established. In addition, trial material in tablet form will be developed and produced. In parallel with this, intensive work is underway to select the most optimal partner to conduct the study with, and interest is high.
In a studio interview with BioStock in June, emphasized the CEO Johan Drott that over 20 pharmaceutical companies have so far shown interest in the project, which can be considered a very good mark for the Lund-based company.
To ensure that an agreement can be signed, Respiratorius collaborates with North American Partner International Inc. which uses its global network to identify stakeholders, a work that has so far gone well. It has also signaled that the partnering work is progressing according to plan despite the ongoing Covid-19 pandemic.
The company wants to make an exit
It is no coincidence, however, that the project seems to be attracting widespread interest. In light of the candidate's solid survival data, the European Medicines Agency has EMA recommended Respiratorius to proceed directly to a Phase III study after positive results in Phase I/IIa, without first having to conduct a Phase IIb study.
In addition, the company has a solid patent portfolio and orphan drug status in the most important markets of Europe and the US. The fact that the company has openly communicated that it has an ambition to make an exit may also have increased interest.
CEO has a good track record for achieving exit
In the interview referred to above, CEO Johan Drott himself reasoned that an initial agreement will likely involve a license for the grantee to continue to run the VAL001 project, associated with an advance payment and milestone-related installment payments.
Drott probably knows what he's talking about, as a deal for VAL001 wouldn't be the first on his resume. In addition to Respiratorius, Johan Drott is also CEO of the privately owned prostate cancer company Diaprost as in January this year sold the rights to its antibody h11B6 to an unnamed leading pharmaceutical company through an option agreement signed back in 2017. The deal has a total contract value in the billions through an upfront payment and research funding of USD 13 million and additional consideration that could amount to USD 90 million, which consists of the option fee together with any future commercial milestone payments.
The Diaprost agreement may be a possible indication of Respiratorius' expectations for an agreement for the VAL001 project.
Other agreements in the industry
At the beginning of 2020 was signed a global collaboration and licensing agreement for tafasitamab between MorphoSys and IncyteIncyte paid MorphoSys $750 million upfront, as well as an equity investment worth $150 million. MorphoSys is also eligible for milestone payments worth up to $1,1 billion, in addition to any royalties from the drug upon market approval.
Another recent deal with DLBCL in focus took place in April when Gilead Sciences Inc. acquired Forty Seven Inc. for USD 4.9 billion and thereby, among other things, secured access to the company's leading drug candidate magrolimab as Gilead sees possibility to be able to position against DLBCL. In early September undertecknade in addition Abbvie and I-Mab an agreement regarding I-Mab's CD47 antibody lemzoparlimab with a total contract value of 2.9 billion USD.
All of these agreements include candidates that are partly developed against DLBCL, but they are still significantly different from VAL001. First, all three of the above-mentioned candidates are antibodies, i.e. immuno-oncology therapies, a pharmaceutical segment that is very popular right now. Second, the Gilead/Forty deal concerns a full-scale acquisition and second, each candidate has a significantly broader target indication than just DLBCL, which is why they address significantly larger markets – and potential revenues.
While acquisitions of other DLBCL candidates indicate strong interest in Respiratorius' main indication, and may help open the eyes of more players to VAL001, it is difficult to estimate a potential deal value. It is likely that a deal may also contain a royalty component, which further complicates a comparison.
Fewer side effects with VAL001
Currently, the most effective DLBCL treatment is the combination therapy R-CHOP. Although the development of innovative drugs is taking place at a rapid pace, according to Respiratorius, these new drugs are very expensive and can cause significant side effects, which is why VAL001 is considered to have several competitive advantages.
Two of Respiratorius' potential success factors are based on the fact that VAL001 is based on a well-established substance, valproic acid, which has been used to treat epilepsy since the 1960s. This means that the safety profile and possible side effects are well known, which is important as the patient group in DLBCL consists of older and therefore more sensitive people. The second factor is that the known safety profile significantly lowers the development risk in the project.
BioStock will follow with interest Respiratorius' continued business development activities and the continued development process with both VAL001 and the company's other candidates, including RESP9000 which is being developed in COPD and asthma.
The content of BioStock's news and analysis is independent, but BioStock's operations are to some extent financed by companies in the industry. This post refers to a company from which BioStock has received funding.