Leap Therapeutics Poised for Breakout with Strategic Review and Sirexatamab Trials

What’s Real / What We Know

Clinical data (sirexatamab = DKN-01, DeFianCe study)

• The Phase 2 DeFianCe study (Part B) showed statistically significant improvements in certain subgroups of colorectal cancer patients (microsatellite‐stable CRC) when treated with sirexatamab + bevacizumab + chemotherapy vs bevacizumab + chemotherapy alone. PR Newswire+2investors.leaptx.com+2
• In patients with high levels of DKK1, PFS (progression‐free survival) was ~ 9.36 vs ~ 5.88 months. HR ≈ 0.47. PR Newswire
• In VEGF-naïve patients, similar benefits; and in patients with liver metastases there was also a benefit. PR Newswire+1
• ORR (overall response rate) by blinded review in some subgroups was meaningfully better. PR Newswire+1
• However, in the full intention-to-treat (ITT) population, results are more mixed: PFS benefit was smaller / non-statistically significant in some analyses; the effect in ORR is stronger in certain biomarker defined subgroups. PR Newswire+1

Financial / Corporate Health

• Revenue: Leap appears to have essentially no meaningful revenue (or very little). Recent reports show revenue ~$0.0 for trailing 12 months. WallStreetZen+2StockAnalysis+2
• Expenses are large: R&D is high, SG&A is high; the company is incurring large losses. For example, in a recent trailing-12-month period, net loss ≈ $60-70 million. StockAnalysis+2PR Newswire+2
• Cash position: As of March 31, 2025, cash and cash equivalents were ~$32.7 million. Leap expects costs from workforce reduction etc. PR Newswire
• They are doing a large cost cut: ~75% workforce reduction. They also are winding down or completing the DeFianCe trial and exploring strategic alternatives (sale, partnerships, etc.). PR Newswire

Market & Stock Price Context

• The stock is low-priced (under a dollar currently). Macrotrends+1
• It has been very volatile and has lost large % over the past years. For instance, Macrotrends shows that its 52-week high was ~$4-5, while current is ~$0.30. Macrotrends

How Orbo’s Prediction Stacks Up vs Reality

Orbo’s prediction (from what you shared) is:

• Price target ≈ $5.50 (from ~$0.28 in July) — that’s an expected gain of ~1,800%.
• Huge upside driven by: success of clinical trials in key subgroups, strategic review (sale/partnership), financial management, etc.

So the question: Is that magnitude of upside plausible? Here are the “yes, but with big caveats” factors, and the risks.

Upside Potential

These are levers that could deliver a strong return if everything breaks right:

1. Positive clinical data & biomarker stratification

• The subgroup data (DKK1-high, VEGF-naïve, etc.) show decent effect sizes, which means if the company can get regulatory agreement (e.g. fast-track, or breakthrough, or strong partners) in a precision medicine setting, the market would reward that.
• Also, shifting to more defined, high‐DKK1 patients (i.e. selecting the population) improves odds.

1. Strategic alternatives

• If Leap can partner with a larger pharma or be acquired (or sell the rights to sirexatamab) at a premium, that could unlock value far above what current valuation implies.

1. Catalysts

• Next major readouts (e.g. longer follow-up, OS data, further subgroup validation).
• Any regulatory signals or breakthrough designation.
• The outcome of the strategic review (sale, licensing).

1. Low base valuation

• Because the stock is currently so depressed and the market has largely discounted many of its risks, there is more room for big upside if favorable events occur (i.e. low expectations mean any good news could have an outsize effect).

Major Risks / What Could Go Wrong

Equally important are the barriers to reaching Orbo’s price target. These are serious:

1. Financial runway is short

• ~$32.7M in cash is not a lot given burn rate. High R&D + SG&A + cost of trials + restructuring + regulatory costs = likely need more capital. If they cannot raise capital (or partner) on favorable terms, dilution is likely.

1. Trial winding down / reduced staff

• The fact that they are reducing workforce by ~75%, and winding down aspects of the trial, suggests the company cannot sustain current scale. That increases risk that trial follow-up, regulatory filings, or scale up will be delayed or compromised.

1. Full population results may disappoint

• So far, the strongest effects are in subgroups. The ITT population results have significance concerns (confidence intervals, p-values that are marginal in some comparisons). If broader populations underperform, the market will likely be unforgiving.

1. Regulatory / Commercial execution risk

• Even with positive data, getting approvals, payer acceptance, market share, commercialization is expensive. A small biotech with limited resources will need strong partners. If partner terms are unfavorable, much of upside could go to the partner, not shareholders.

1. Competition / risk of being leap-frogged

• Oncology is a very competitive field. Other companies are also developing treatments in CRC, etc. If someone else comes up with better data, or a competitor moves faster, that can reduce LPTX’s window.

1. Dilution

• To execute on further trials, or commercial launch, or even to continue operations, they may need more funding, meaning possible issuance of shares, which dilutes current holders (especially painful when share price is low).

1. Market sentiment / biotech risk

• Biotech investors are often hypersensitive to “expectations vs reality”. Negative side effects, regulatory setbacks, or failure to partner can lead to very steep drops.

My Take: Is $5.50 Possible?

Putting this all together:

• Yes, it’s technically possible, especially if multiple things go right: strong subgroup clinical data, securing a good strategic partner or outright acquisition, favorable regulatory feedback, avoiding dilution, managing to stretch the cash runway, etc.
• But $5.50 is a very ambitious target. That would imply not only that the company is believed to have a near-term commercial path, but that market perception shifts dramatically.

If I were to assign odds (informally) I’d say:

• Low to moderate probability of some big upside (say 2-10× from current levels) — if the subgroup results and strategic deals are good.
• Much lower probability (say <10%) of reaching >15-20× (~$5.50 from ~$0.30) in the timeframe Orbo suggests (within a few months). It’s not impossible, but many moving parts need to go right.

Ok, LPTX is on an continued upward move. It’s up 66% in a week.