Form 424B2 Calyxt, Inc.

As of December 31, 2021, the Company had $14.3 million of cash, cash equivalents,
and restricted cash. The Company’s restricted cash is associated with its equipment financing leases and was $1.0 million as of September 30, 2021 and $0.6 million as of December 31, 2021. Current liabilities were $5.1 million as
of September 30, 2021 and $4.1 million as of December 31, 2021.

The Company anticipates that it will continue to generate
losses for the next several years. Over the longer term and until the Company can generate cash flows sufficient to support its operating capital requirements, it expects to finance a portion of future cash needs through (i) cash on hand,
(ii) commercialization activities, which may result in various types of revenue streams from (a) future product development agreements and technology licenses, including upfront and milestone payments, annual license fees, and royalties;
and (b) product sales from its proprietary BioFactory production system; (iii) government or other third-party funding, which the Company expects to be more readily available if Cellectis were to own less than 50 percent of

the Company’s common stock, (iv) public or private equity or debt financings, or (v) a combination of the foregoing. However, additional capital
may not be available on reasonable terms, if at all.

For example, the Company currently expects that based on the Company’s public
float, as of the date of the filing of the Company’s Annual Report for the year ended December 31, 2021, the Company will only permitted to utilize a “shelf” registration statement, including the registration statement under
which the Company’s ATM Facility is operated, subject to Instruction I.B.6 to Form S-3, which is referred to as the “baby shelf” rules. From the date of the filing of the Annual Report for the
year ended December 31, 2021 and for so long as the Company’s public float remains less than $75,000,000, it will not be permitted to sell more than the equivalent of one-third of its public float
during any 12 consecutive months pursuant to the baby shelf rules. Although alternative public and private transaction structures are expected to be available, these may require additional time and cost, may impose operational restrictions on the
Company, and may not be available on attractive terms.

The Company’s current operating plans reflect a modest level of payments from
customers for commercial activities in 2022 and planned spending to support the further scale up of the production of the BioFactory production system. The Company will require additional liquidity through public or private equity or debt financings
to continue operations under this business plan over the next 12 months.

If the Company is unable to raise additional capital in a
sufficient amount or on acceptable terms, management may be required to implement various cost reduction and other cash-focused measures to manage liquidity and the Company may have to significantly delay, scale back, or discontinue its development
or commercialization activities. Failure to receive additional funding could cause the Company to cease operations, in part or in full. If the Company raises additional funds through the issuance of additional debt or equity securities, it could
result in dilution to its existing stockholders and increased fixed payment obligations, and these securities may have rights senior to those of the Company’s shares of common stock. Any of these events could significantly harm the
Company’s business, financial condition, and prospects.

The Company faces significant competition and many of its competitors have
substantially greater financial, technical, and other resources than Calyxt.

The market for products developed with synthetic
biology is highly competitive, and the Company faces significant direct and indirect competition in several aspects of its business. See “Business—Competition”. Many of these competitors have substantially greater financial,
technical, marketing, sales, distribution, and other resources than the Company. Many of the Company’s competitors engage in ongoing R&D, and technological developments by its competitors could render the Company’s technology less
competitive or obsolete, resulting in reduced revenues compared to expectations. As a result, the Company may be unable to compete successfully against its current or future competitors, which may result in reductions in revenue, reduced margins,
and the inability to achieve market acceptance for its products. The Company expects to continue to face significant competition.

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